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CORK Bibliography: Alcohol (Acute Effects)

103 citations. 2007 to present

Prepared: June 2009

Aasebo W; Erikssen J; Jonsbu J; Stavem K. ECG changes in patients with acute ethanol intoxication. Scandinavian Cardiovascular Journal 41(2): 79-84, 2007. (24 refs.)

Objectives. To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. Design. We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. Results. In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and < 0.0001 for P wave, PR, QRS and QTc intervals. n = 32). Conclusions. Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.

Acosta MC; Eissenberg T; Nichter M; Nichter M; Balster RL. Characterizing early cigarette use episodes in novice smokers. Addictive Behaviors 33(1): 106-121, 2008. (45 refs.)

Retrospective self-report data indicate that early cigarette use episodes may be important predictors of smoking. Unfortunately, recall of early experiences are confounded with current smoking, The current study is the first to examine early cigarette use episodes (EUEs) prospectively in novice smokers (less than 15 lifetime cigarettes). Smoking amount, context and subjective experiences for up to five of the first cigarette episodes during their first year of college were collected using weekly internet-based questionnaires and structured interviews. Data were obtained on 538 early cigarette use episodes from 163 students. These early cigarette use episodes generally occurred within a social/party context; over 90% of occurred when participants were with other people who were smoking and over 65% occurred while participants were drinking alcohol. Subjective effects across episodes were reported as generally mild and factor analysis yielded Positive, Negative and Sensory/Peripheral effects scales. Subjective effects were related to the amount smoked and inhalation, whereas early cigarette use episodes context, including alcohol use and social context, was not. This study demonstrates that it is possible to study early cigarette use episodes in college students within days or weeks of their occurrence and that most of these occur in social settings with the concurrent use of alcohol.

Addicott MA; Marsh-Richard DM; Mathias CW; Dougherty DM. The biphasic effects of alcohol: Comparisons of subjective and objective measures of stimulation, sedation, and physical activity. Alcoholism: Clinical and Experimental Research 31(11): 1883-1890, 2007. (44 refs.)

Background: Alcohol produces biphasic effects of both stimulation and sedation. Sensitivity to these effects may increase the risk for the development of alcoholism. Alcohol-induced changes in stimulation and sedation are commonly assessed with self-report questionnaires in human research and with physical activity monitoring in animal research. However, little is known about the effects of alcohol on physical activity or the relationship between physical activity and subjective self-report measures of stimulation and sedation following alcohol consumption in humans. Methods: Thirty healthy men and women (n = 15 each) from 21 to 38 years old completed daily measurements of physical activity and self-reports of stimulation and sedation following alcohol or placebo consumption. Across each of the four experimental days, all participants consumed a placebo, 0.4, 0.6, or 0.8 g/kg dose of 95% alcohol in a counterbalanced order. Breath alcohol concentrations, physical activity levels, and self-reported stimulation and sedation were measured at baseline and on the ascending and descending limbs of the breath alcohol concentration (BrAC) curve. Results: All alcohol doses increased physical activity, but these increases were time- and dose-dependent. Increases in physical activity lasted across both ascending and descending limbs of the BrAC curve. Following the 0.6 g/kg dose, both physical activity and self-reported stimulation increased during the ascending BrAC. Separate analyses of self-reported sedation scores indicated that alcohol consumption also increased sedation for the 0.6 and 0.8 g/kg doses. Physical activity was not significantly correlated with either self-reported stimulation or sedation at any time point. Conclusions: These findings suggest that assessments of subjectively measured stimulation and sedation and objectively measured physical activity each assess unique aspects of the effects of alcohol. Used simultaneously, these measures may be useful for examining underlying mechanisms of the effects of alcohol on behavior.

Allen AJ; Meda SA; Skudlarski P; Calhoun VD; Astur R; Ruopp KC et al. Effects of alcohol on performance on a distraction task during simulated driving. Alcoholism: Clinical and Experimental Research 33(4): 617-625, 2009. (32 refs.)

Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks. We studied this phenomenon, using a dual-task paradigm, involving performance of a visual oddball (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI (fMRI) studies of the VO task have shown activation in the anterior cingulate, hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases in activation of these areas during VO performance. Forty healthy social drinkers were administered 3 different doses of alcohol, individually tailored to their gender and weight. Participants performed a VO task while operating a virtual reality driving simulator in a 3T fMRI scanner. Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance, primarily in hippocampus, anterior cingulate, and dorsolateral prefrontal areas, with the least activation occurring during the high dose. Behavioral analysis showed a dose-dependent linear increase in reaction time, with no effects associated with either correct hits or false alarms. In all dose conditions, driving speed decreased significantly after a VO stimulus. However, at the high dose this decrease was significantly less. Passenger-side line crossings significantly increased at the high dose. These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions, which are involved with attentional processing/decision-making. Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving.

Ando S; Iwata T; Ishikawa H; Dakeishi M; Murata K. Effects of acute alcohol ingestion on neuromotor functions. Neurotoxicology 29(4): 735-739, 2008. (36 refs.)

To scrutinize the neuromotor effects of acute alcohol ingestion, postural sway, hand tremor, and reaction time were measured before and after alcohol or juice ingestion in 13 healthy volunteers at 20-22 years (mean 20.7) of age. The dose of ethanol consumed by the subjects (mean +/- S.D.) was 0.59 +/- 0.07 g/kg body weight, and the blood ethanol concentrations were estimated to be 0.86 +/- 0.23 g/l at 30 min after ethanol ingestion: 0.88 +/- 0.19 g/l at 70 min: 0.74 +/- 0.27 g/l at 130 min. The 1-h and 2-h changes in sway area, total transversal sway (Dx), and Dx at 0-1 Hz with eyes closed were significantly larger after alcohol ingestion than after juice ingestion. Similarly, the 2-h changes in sway area, total Dx, and Dx at 0-1 Hz with eyes open were significantly larger after alcohol ingestion than after juice ingestion. No significant differences were seen between alcohol and juice ingestion regarding changes in hand tremor or reaction time. These data suggest that the static balance due to acute alcohol ingestion is characterized mainly by transversal sway of low frequency (0-1 Hz) with eyes closed, which seems to differ from the characteristics of postural sway in alcoholics.

Austin JL; Smith JE. Drinking for negative reinforcement: The semantic priming of alcohol concepts. Addictive Behaviors 33(12): 1572-1580, 2008. (54 refs.)

Cognitive models of alcohol abuse posit that the context typically associated with alcohol use, such as negative affect, implicitly activates alcohol use cognitions, which in turn leads to alcohol consumption. We selected 40 undergraduate women based upon their alcohol use and reported anxiety sensitivity, and proposed that drinking for the purpose of negative reinforcement would predict increased semantic priming between anxiety and alcohol concepts. A lexical decision task compared the response latencies of alcohol targets preceded by anxiety words to those same targets preceded by neutral words (anxiety-alcohol priming). Level of anxiety sensitivity did not relate to anxiety-alcohol priming, but drinking following social conflict was associated with increased anxiety-alcohol priming. This study specifically suggests that the contextual antecedents to drinking behavior relate to the organization of semantic information about alcohol, and more generally supports cognitive models of substance abuse.

Barry H; Appel J. Early preclinical studies of discriminable sedative and hallucinogenic drug effects. (review). Psychopharmacology 203(2): 193-201, 2009. (80 refs.)

One important technique in behavioral pharmacology is to train laboratory animals to discriminate between a psychoactive drug effect and a nondrug condition. Tests with different drugs have identified several categories of drugs that have different discriminable effects. The two authors describe and discuss the early research on discriminable effects of sedative and hallucinogenic drugs and their acquaintance with each other at Yale University prior to their early and frequent Publications on discriminable drug effects. Herb Barry studied sedative drugs primarily and Jim Appel studied hallucinogenic drugs. Sedative drugs include ethyl alcohol, barbiturates, and benzodiazepines. Their discriminable effects are largely attributable to the activation of an inhibitory neurotransmitter, gamma-amino butyric acid. Alcohol has the most pervasive effect in accordance with the high dose required to alter behavior. Hallucinogenic drugs include lysergic acid diethylamide and mescaline. They increase the activity of the neurotransmitter 5-hydroxytryptamine and, perhaps, dopamine in the central nervous system (CNS). In spite of their relatively low concentrations in the brain, both of these neurotransmitters have many important behavioral effects. Various sedative drugs cause a discriminable decrease in the function of the CNS. Different types of sedatives can be discriminated from each other. Indole and phenylethylamine hallucinogens have potent discriminative stimulus properties, which are related to the actions of biogenic amine neurotransmitters in the CNS.

Batki SL; Leontieva L; Dimmock JA; Ploutz-Snyder R. Negative symptoms are associated with less alcohol use, craving, and "high" in alcohol dependent patients with schizophrenia. Schizophrenia Research 105(1-3): 201-207, 2008. (22 refs.)

Background: Alcohol use disorders (AUDs) frequently co-occur with and exacerbate schizophrenia, yet the specific relationships between schizophrenia symptoms and alcohol use remain unclear. Methods: PANSS scores were correlated with measures of alcohol and other substance use in patients with schizophrenia-spectrum disorders and AUDs entering a trial of monitored naltrexone treatment. Data were analyzed from the first 80 participants; 55% had schizophrenia and 45% had schizoaffective disorder. All had AUDs; 95% had alcohol dependence and 5% alcohol abuse; 34% also had cannabis abuse/dependence and 31% cocaine abuse/dependence. Results: PANSS Negative scores were inversely correlated with Addiction Severity Index alcohol composite scores, alcohol craving, quality of alcohol "high" (euphoria), and with frequency of cannabis use. An exploratory analysis indicated that the negative symptoms that may most strongly con-elate with less alcohol use, craving and/or euphoria were passive/apathetic social withdrawal, blunted affect, difficulty in abstract thinking, and stereotyped thinking. Higher PANSS Composite scores, indicating the predominance of positive over negative PANSS symptoms, correlated with more alcohol craving and cannabis use. Higher PANSS General scores were associated with more alcohol craving. Conclusions: These findings extend previous reports of the association of negative schizophrenia symptoms with less alcohol and substance use to patients with AUDs and indicate that this relationship also includes less alcohol craving and less alcohol euphoria. The findings may also provide some initial evidence that specific negative symptoms may be keys to these relationships.

Bizzarri JV; Rucci P; Sbrana A; Gonnelli C; Massei GJ; Ravani L; Girelli M; Dell'Osso L; Cassano GB. Reasons for substance use and vulnerability factors in patients with substance use disorder and anxiety or mood disorders. Addictive Behaviors 32(2): 384-391, 2007. (18 refs.)

This cross-sectional study examined the reasons for substance use and the presence of vulnerability factors such as substance sensitivity, sensation seeking, and symptoms related to the attention deficit hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) and comorbid mood and anxiety disorders by using the Structured Clinical Inter-view for the Spectrum of Substance Use (SCI-SUBS), a novel instrument designed to explore the spectrum of substance use and its clinical correlates. Study participants included 61 patients with SUD and mood or anxiety disorder, and two comparison groups including 35 patients with SUD only and 50 controls not in treatment for mental disorders or SUD. We found that patients with co-morbid mood or anxiety disorder had significantly higher scores on the SCI-SUBS domains 'substance sensitivity' and 'self-medication' as compared to those with SUD only. Scores on 'sensation seeking' and 'ADHD' domains were similar between both groups of patients and higher than in controls. Patients with comorbid mood or anxiety disorders showed a higher sensitivity to substances and were more prone to self-medication than those with SUD only. These characteristics should be taken into account in the diagnostic assessment and in long-term treatment to decrease the risk of relapse.

Borghese CM; Harris RA. Studies of ethanol actions on recombinant delta-containing gamma-aminobutyric acid type A receptors yield contradictory results. Alcohol 41(3): 155-162, 2007. (48 refs.)

The gamma-aminobutyric acid type A receptors (GABA(A)-Rs) display a wide variety of subunit combinations. Drugs such as benzodiazepines have shown differential effects based on GABA(A)-R subunit composition. Actions of alcohols and volatile anesthetics generally do not vary markedly with subunit composition, with low concentrations of ethanol being poor modulators of these receptors. Recent studies showed alpha(-)(4/6) and delta-containing GABA(A)-Rs (located extrasynaptically and responsible for tonic currents in selective brain regions) presenting high sensitivity to low concentrations of ethanol, but these results have not been obtained in other laboratories. We carried out additional experiments varying the receptor level of expression, and GABA and ethanol concentration, but no sensitivity to low concentrations of ethanol was detected. We will discuss these results and attempt an analysis of the possible causes for the discrepancies.

Brand-Miller JC; Fatima K; Middlemiss C; Bare M; Liu V; Atkinson F. Effect of alcoholic beverages on postprandial glycemia and insulinemia in lean, young, healthy adults. American Journal of Clinical Nutrition 85(6): 1545-1551, 2007. (25 refs.)

Background: Ethanol's ability to inhibit gluconeogenesis might reduce postprandial glycemia in realistic meal settings. Objective: The objective was to explore the effect of 3 types of alcoholic beverages consumed alone, with a meal, or 1 h before a meal on postprandial glycemia in healthy subjects. Design: In study 1, isoenergetic (1000 kJ) servings of beer, white wine, and gin were compared with a 1000-kJ portion of white bread. In study 2, the same servings were compared with water as an accompaniment to a bread meal. In study 3, 20-g alcohol portions were served as a premeal drink. Fingertip capillary blood samples were taken at regular intervals over 2-3 h. Results: In study 1, the mean (SE) glucose scores for beer (58 +/- 11), wine (7 +/- 3), and gin (10 +/- 5) were significantly lower (P < 0.001) than those for bread (= 100). In study 2, meals consumed with beer (84 +/- 11; P = 0.03), wine (63 +/- 6; P < 0.001), and gin (80 +/- 12; P = 0.007) produced less glycemia than did the meal consumed with water (= 100). In study 3, all 3 beverages reduced the postprandial glycemic response to the subsequent meal (67 +/- 5, 75 +/- 6, and 78 +/- 4 with the beer, wine, and gin trials, respectively; P < 0.003). Conclusion: In realistic settings, alcoholic beverage consumption lowers postprandial glycemia by 16-37%, which represents an unrecognized mechanism by which alcohol may reduce the risk of chronic disease.

Buttari B; Profumo E; Mancinelli R; Incani UC; Tosti ME; Attilia ML et al. Chronic and acute alcohol exposure prevents monocyte-deried dendritic cells from differentiating and maturing. International Journal of Immunopathology and Pharmacology 21(4): 929-939, 2008. (30 refs.)

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alciDCs). Alc-iDCs showed fewer CD1a(+) cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naive allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

Cannon R; Lubar J; Baldwin D. Self-perception and experiential schemata in the addicted brain. (review). Applied Psychophysiology and Biofeedback 33(4): 223-238, 2008. (176 refs.)

This study investigated neurophysiological differences between recovering substance abusers (RSA) and controls while electroencephalogram (EEG) was continuously recorded during completion of a new assessment instrument. The participants consisted of 56 total subjects; 28 RSA and 28 non-clinical controls (C). The participants completed the self-perception and experiential schemata assessment (SPESA) and source localization was compared utilizing standardized low-resolution electromagnetic tomography (sLORETA). The data show significant differences between groups during both the assessment condition and baselines. A pattern of alpha activity as estimated by sLORETA was shown in the right amygdala, uncus, hippocampus, BA37, insular cortex and orbitofrontal regions during the SPESA condition. This activity possibly reflects a circuit related to negative perceptions of self formed in specific neural pathways. These pathways may be responsive to the alpha activity induced by many substances by bringing the brain into synchrony if only for a short time. In effect this may represent the euphoria described by substance abusers.

Chaplin TM; Hong K; Bergquist K; Sinha R. Gender differences in response to emotional stress: An assessment across subjective, behavioral, and physiological domains and relations to alcohol craving. Alcoholism: Clinical and Experimental Research 32(7): 1242-1250, 2008. (59 refs.)

Background: Women and men are at risk for different types of stress-related disorders, with women at greater risk for depression and anxiety and men at greater risk for alcohol-use disorders. The present study examines gender differences in emotional and alcohol craving responses to stress that may relate to this gender divergence in disorders. Methods: Healthy adult social drinkers (27 men, 27 women) were exposed to individually developed and calibrated stressful, alcohol-related, and neutral-relaxing imagery, 1 imagery per session, on separate days and in random order. Subjective emotions, behavioral/bodily responses, cardiovascular arousal [heart rate (HR), blood pressure (BP)], and self-reported alcohol craving were assessed. Results: Women reported and displayed greater sadness and anxiety following stress than men and men had greater diastolic BP response than women. No gender differences in alcohol craving, systolic BP or HR were observed. Subjective, behavioral, and cardiovascular measures were correlated in both genders. However, for men, but not women, alcohol craving was associated with greater subjective emotion and behavioral arousal following stress and alcohol cues. Conclusions: These data suggest that men and women respond to stress differently, with women experiencing greater sadness and anxiety, while men show a greater integration of reward motivation (craving) and emotional stress systems. These findings have implications for the gender-related divergence in vulnerability for stress-related disorders, with women at greater risk for anxiety and depression than men, and men at greater risk for alcohol-use disorders than women.

Chappell AM; Weiner JL. Relationship between ethanol's acute locomotor effects and ethanol self-administration in male long-Evans rats. Alcoholism: Clinical and Experimental Research 32(12): 2088-2099, 2008. (67 refs.)

Human studies have suggested an important relationship between ethanol sensitivity and risk of alcoholism. These studies have led some to hypothesize that a low initial sensitivity to ethanol's depressant effects and/or an elevated response to ethanol's stimulant effects may represent important risk factors associated with the development of abusive drinking behavior. Unfortunately, elucidating neurobiologic mechanisms that may underlie these relationships between ethanol sensitivity and ethanol drinking have been hampered by difficulties in modeling some of these interactions in animals. In this study, we re-examined some of these relationships in an outbred strain of rats using continuous access two-bottle choice drinking and a limited-access operant procedure that engenders pharmacologically relevant levels of ethanol intake and permits the discrete assessment of appetitive and consummatory measures of ethanol drinking behavior. Twenty-three male Long-Evans rats were habituated to a locomotor activity box and then tested for their response to a stimulant (0.5 g/kg) and depressant (1.5 g/kg) ethanol dose. Rats were then trained to complete a lever pressing requirement to gain access to 10% ethanol for 20-minute sessions conducted 5 d/wk for 5 weeks. Appetitive behavior was assessed after 2.5 and 4.5 weeks using 20-minute extinction trials in which ethanol was not presented and lever responses were recorded. Home-cage ethanol preference was also assessed prior to and immediately following the 5-week self-administration regimen using a continuous access, two-bottle choice procedure. A significant increase in home-cage ethanol preference was observed following the self-administration procedure, however, neither measure of ethanol preference correlated with average daily ethanol intake during the operant self-administration sessions or with initial sensitivity to ethanol's stimulant or depressant effects. Notably, a significant negative correlation was observed between sensitivity to ethanol's locomotor depressant effect and daily intake during the operant self-administration sessions. No significant relationships were noted between sensitivity to ethanol's locomotor effects and extinction responding. The results of these studies suggest that the well-established relationship between a low level of response to ethanol and increased ethanol consumption reported in human studies can be observed in an outbred rodent strain using a limited-access operant self-administration procedure, but not with home-cage ethanol drinking.

Corbin WR; Gearhardt A; Fromme K. Stimulant alcohol effects prime within session drinking behavior. Psychopharmacology 197(2): 327-337, 2008. (55 refs.)

Rationale: Individual differences in subjective alcohol effects have been shown to differ by risk status (e.g., family history of alcoholism) and to predict future risk for alcohol-related problems. Presumably, individual differences in both stimulant and sedative responses affect the rewarding value of drinking which, in turn, impacts future drinking behavior. Although plausible, this theoretical model is largely untested. Objectives The current study attempted to provide experimental evidence for the impact of subjective alcohol responses on within session drinking behavior. Materials and methods Using a placebo-controlled between-subjects alcohol administration paradigm, experiences and evaluations of stimulant and sedative alcohol effects (after a target dose of 0.06 g%) were assessed as predictors of ad-libitum consumption in the context of anticipatory stress. Results: Analyses indicated that an initial dose of alcohol increased experiences of both stimulation and sedation although stimulant effects were evaluated much more positively. In addition, stimulant effects after a priming dose predicted further consumption, whereas sedative effects did not. Conclusions: At least among moderate to heavy drinking college students, stimulant alcohol effects are more reinforcing and predict within session drinking behavior under social stress. Increased attention should be given to stimulant alcohol effects as a risk factor for excessive consumption in this population. Incorporating information about stimulant alcohol effects in prevention and intervention programs may also be important if additional research supports the current results.

Croissant B; Dernmel R; Rist F; Olbrich R. Exploring the link between gender, sensation seeking, and family history of alcoholism in cortisol stress-response dampening. Biological Psychology 79(2): 268-274, 2008. (55 refs.)

Many studies have demonstrated an inverse association between cortisol and risk-taking behaviors, with high-sensation seekers (HSS) showing lower cortisol levels. We investigated the potential link between sensation seeking (SS) and stress-induced stress responses, as well as alcohol-induced stress-response-dampening (SRD) effects in cortisol. First, we hypothesized that HSS would show inverse SRD effects in cortisol. Second, we hypothesized that females would display similar SRD effects to males. Third, we hypothesized an independent relationship between SS and family history (FH) with regard to alcohol-induced SRD effects in cortisol. 86 healthy men and women participated in two laboratory sessions, receiving alcohol in one of the two. Experimental stress paradigms were administered and serum cortisol was measured. SRD effects in cortisol developed for both genders in low-sensation seekers (LSS), but not in HSS. This study contributes to current literature by (1) supporting the association between SS and cortisol, (2) demonstrating that SRD effects in cortisol of females is inversely related to SS, and (3) demonstrating an independent relationship between SS and FH with regard to alcohol-induced SRD effects in cortisol.

Dougherty DM; Marsh-Richard DM; Hatzis ES; Nouvion SO; Mathias CW. A test of alcohol dose effects on multiple behavioral measures of impulsivity. Drug and Alcohol Dependence 96(1-2): 111-120, 2008. (38 refs.)

Background: Acute alcohol administration affects impulsive behavior, although these effects vary as a function of alcohol dose, assessment instrument, and time of measurement following administration. Methods: We concurrently examined the dose-dependent effects of alcohol on three distinct types of impulsivity tasks (continuous performance [IMT], stop-signal [GoStop], and delay-discounting [SKIP] tasks). Ninety healthy alcohol drinkers were assigned to one of the three task groups (n = 30 each), each group experienced placebo, 0.2, 0.4, 0.6, and 0.8 g/kg alcohol doses across 5 experimental days, and task performance was assessed at 0.5 h before and 0.25, 1.0, and 2.0 h after alcohol administration. We hypothesized that impulsive responding on all tasks would be increased by acute alcohol administration both across time and during the peak BrAC, but the magnitude would depend on the task being tested. Analyses included the time course and the peak BrAC effects. Task comparisons of peak behavioral changes following each dose are illustrated using standardized scores. Results: While alcohol consumption increased impulsive responding during all three tasks to some extent, our hypothesis was only partially supported. During the IMT, the 0.6 and 0.8 g/kg doses produced increased impulsive responding across time and at the peak BrAC. However, during the GoStop and SKIP, impulsivity increased across time regardless of the alcohol dose size, with no differences in impulsive responding among dose conditions at peak BrAC. Conclusions: This study demonstrated alcohol-induced changes in impulsivity are not uniformly affected by alcohol. These data, in conjunction with previous studies, further support that impulsivity is not a unitary construct.

Duranceaux NCE; Schuckit MA; Luczak SE; Eng MY; Carr LG; Wall TL. Ethnic differences in level of response to alcohol between Chinese Americans and Korean Americans. Journal of Studies on Alcohol and Drugs 69(2): 227-234, 2008. (47 refs.)

Objective: Koreans have higher rates of alcohol-use disorders and family history of alcoholism, compared with Chinese. These differences likely reflect both environmental and genetic influences. One genetically influenced characteristic that may contribute to these ethnic differences is level of response to alcohol. Variant alleles of aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH1B) genes are prevalent in individuals of Asian heritage and have been associated with an increased level of response to alcohol and a decreased risk for alcohol dependence. Additionally, a low level of response to alcohol is more common in individuals with a first-degree family history of alcoholism and is predictive of increased risk for this disorder. It also is possible that sociocultural factors have an impact on an individual's response to alcohol. The current study examined self-report level of response to alcohol, ALDH2 and ADH1B, country of origin, and family history of alcoholism in 154 Chinese- and 181 Korean-American college students. Method: Participants were evaluated via in-person interviews and genotyped at the ALDH2 and ADH1B loci. Results: Ethnicity was significantly related to level of response to alcohol, with Koreans having a lower self-reported level of response than Chinese. This relationship remained significant after considering the effects of gender, height, weight, quantity and frequency of alcohol consumption (over the previous 90 days), ALDH2 genotype, ADH1B genotype, country of origin, and first-degree family history of alcohol dependence. Conclusions: The results suggest that a low level of response to alcohol may contribute to the increased risk for alcohol abuse and dependence found in Koreans, relative to Chinese. More research is needed to determine additional factors that may be contributing to the low alcohol response and high rates of alcoholism in Koreans.

El-Guindy NBD; de Villiers WJ; Doherty DE. Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance. Alcohol 41(5): 335-345, 2007. (68 refs.)

Previous studies have shown that alcohol (ethanol [EtOH]) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by downregulating the expression of proinflammatory mediators while simultaneously upregulating anti-inflammatory mediators. EtOH was administered to the mice 0.5 h prior to an intratracheal injection of Escherichia coli lipopolysaccharide (LPS). The animals were killed either 4 or 24 h after LPS to recover plasma, lungs, and bronchoalveolar lavage fluid. Lung inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, macrophage inhibitory factor (MIF), IL-10, TGF-beta, and receptors for TNF-alpha, IL-1 beta, IL-6, and TGF-beta as well as glycoprotein (gp) 130 and corticosterone (CS) levels were evaluated at mRNA and protein level. While the mRNA expression and the soluble TNF-Rp55 levels were significantly upregulated by EtOH, LPS-induced TNF-alpha activity, TNF-Rp55 mRNA expression, and soluble TNF-Rp55 levels were significantly suppressed. The LPS-induced expression of IL-1 beta, IL-6, MIF, gp 130, and receptors IL-IRI, IL-IRIL and IL-6R alpha were also significantly impaired by EtOH. EtOH increased significantly the basal IL-10 activity at 3 h, which continued to remain elevated even at 24 h. The EtOH effect on IL-10 activity persisted even in LPS-challenged mice. EtOH and LPS augmented lung CS levels independently of each other. EtOH suppressed upregulation of TGF-beta 1 mRNA expression by LPS and blocked completely LPS-induced TGF-beta 1 secretion. In conclusion, the data suggest that the suppression of acute lung inflammation by EtOH intoxication is largely due to impairment by EtOH of proinflammatory cytokine signaling at the levels of cytokine expression and secretion as well as receptor expression and soluble receptor activity. The augmentation by EtOH of anti-inflammatory mediators' secretion most likely shifts the cytokine balance in the anti-inflammatory direction.

Enrico P; Sirca D; Mereu M; Peana AT; Lintas A; Golosio A et al. Acetaldehyde sequestering prevents ethanol-induced stimulation of mesolimbic dopamine transmission. Drug and Alcohol Dependence 100(3): 265-271, 2009. (38 refs.)

Acetaldehyde (ACID) has been postulated to mediate some of the neurobehavioral effects of ethanol (EtOH). In this study we sought to evaluate whether the stimulatory effects of EtOH on mesolimbic dopamine (DA) transmission are affected by the administration of ACID-sequestering agent D-penicillamine (Dp). To this end we studied the effect of EtOH and ACD in the rat mesoaccumbens pathway by in vivo microdialysis in the nucleus accumbens shell (NAccs), and by single cell extracellular recordings from antidromically identified mesoaccumbens DA neurons in the ventral tegmental area (VTA). Both EtOH (1 g/kg) and ACD (20 mg/kg) administration increased DA levels in the NAccs and increased the activity of mesoaccumbens DA neurons. Pretreatment with Dp (50 mg/kg i.p. 1 h before drug challenge) prevented both EtOH- and ACD-induced stimulation of the DA mesolimbic system without affecting morphine stimulatory actions. These observations add further support to the notion that EtOH-derived ACID stimulates the mesolimbic DA system and is essential in EtOH-incluced stimulation of the DA mesoaccumbens system. We conclude that modulation of ACD bioavailability may influence the addictive profile of EtOH by decreasing its psychotropic effects and possibly leading the way to new pharmacological treatments of alcoholism.

Farris SR; Ostafin BD. Alcohol consumption primes automatic alcohol-approach associations. American Journal of Drug and Alcohol Abuse 34(6): 703-711, 2008. (33 refs.)

Objective: There is increasing evidence that automatic mental processes play a role in problematic alcohol use. Although previous research has shown that alcohol consumption can prime alcohol-seeking behavior in animals and humans, little research has examined whether alcohol consumption activates automatic alcohol-related cognitions. The current study was designed to examine the effects of alcohol consumption on the activation of automatic alcohol motivation as measured by a reaction time task. Method: Eighty-five at-risk drinkers participated in the study, which began with a baseline measure of automatic alcohol motivation, after which participants completed a taste-test in which they could consume as much beer as they liked for 10 minutes. Following an absorption period, participants completed the measure of automatic alcohol motivation for a second time. Results: A partial correlation analysis indicated that amount of alcohol consumed predicted stronger automatic alcohol motivation when controlling for the baseline level of automatic alcohol motivation. Conclusion: The findings suggest that alcohol consumption may prime the automatic mental processes that have been shown to contribute to problematic alcohol use.

Feinberg-Zadek PL; Martin G; Treistman SN. BK channel subunit composition modulates molecular tolerance to ethanol. Alcoholism: Clinical and Experimental Research 32(7): 1207-1216, 2008. (38 refs.)

Background: The large conductance calcium-activated potassium channel (also called BK channel or Slo channels) is a well-studied target of alcohol action, and plays an important role in behavioral tolerance. Methods: Using patch clamp electrophysiology, we examined human BK channels expressed in HEK293 cells to test whether tolerance to ethanol occurs in excised patches and whether it is influenced by subunit composition. Three combinations were examined: hSlo, hSlo + beta(1), and hSlo + beta(4). Results: The 2 components of BK alcohol adaptation (Component 1: rapid tolerance to acute potentiation, and Component 2: a more slowly developing decrease in current density) were observed, and varied according to subunit combination. Using a 2-exposure protocol, Component 1 tolerance was evident in 2 of the 3 combinations, because it was more pronounced for hSlo and hSlo + beta(4). Conclusions: Thus, rapid tolerance in human BK occurs in cell-free membrane patches, independent of cytosolic second messengers, nucleotides or changes in free calcium. Alcohol pretreatment for 24 hours altered subsequent short-term plasticity of hSlo + beta(4) channels, suggesting a relationship between classes of tolerance. Finally, Component 2 reduction in current density showed a striking dependency on channel composition. Twenty-four hour exposure to 25 mM ethanol resulted in a down-regulation of BK current in hSlo and hSlo + beta(4) channels, but not in hSlo + beta(1) channels. The fact that hSlo + beta(1) channels show less sensitivity to acute challenge, in conjunction with less Component 1 and Component 2 tolerance, suggests subunit composition is an important factor for these elements of alcohol response.

Filbey FM; Claus E; Audette AR; Niculescu M; Banich MT; Tanabe J et al. Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry. Neuropsychopharmacology 33(6): 1391-1401, 2008. (68 refs.)

A growing number of imaging studies suggest that alcohol cues, mainly visual, elicit activation in mesocorticolimbic structures. Such findings are consistent with the growing recognition that these structures play an important role in the attribution of incentive salience and the pathophysiology of addiction. The present study investigated whether the presentation of alcohol taste cues can activate brain regions putatively involved in the acquisition and expression of incentive salience. Using functional magnetic resonance imaging, we recorded BOLD activity while delivering alcoholic tastes to 37 heavy drinking but otherwise healthy volunteers. The results yielded a pattern of BOLD activity in mesocorticolimbic structures (ie prefrontal cortex, striatum, ventral tegmental area/substantia nigra) relative to an appetitive control. Further analyses suggested strong connectivity between these structures during cue-elicited urge and demonstrated significant positive correlations with a measure of alcohol use problems (ie the Alcohol Use Disorders Identification Test). Thus, repeated exposure to the taste alcohol in the scanner elicits activation in mesocorticolimbic structures, and this activation is related to measures of urge and severity of alcohol problems.

Filbey FM; Ray L; Smolen A; Claus ED; Audette A; Hutchison KE. Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes. Alcoholism: Clinical and Experimental Research 32(7): 1113-1123, 2008. (47 refs.)

Background: Studies suggest that polymorphisms in the D4 dopamine receptor (DRD4) and opioid receptor, mu 1 (OPRM1) genes are involved in differential response to the effects of alcohol and to alcohol cues. However, to date, the mechanisms that underlie these differences remain largely unknown. Methods: Using functional magnetic resonance imaging, hemodynamic response in mesocorticolimbic structures after exposure to alcohol tastes was contrasted with a control taste and compared between DRD4 variable number of tandem repeats (VNTR) genotypes and OPRM1 A118G genotypes. Additionally, the effects of a priming dose of alcohol on this response were examined. Results: The results indicated that DRD4 VNTR > 7 repeat individuals (DRD4.L) had significantly greater response to alcohol cues in the orbitofrontal cortex, anterior cingulate gyrus, and striatum compared with individuals with < 7 repeats (DRD4.S) prior to a priming dose of alcohol (p < 0.05), but not after a priming dose. In the OPRM1 comparisons, results showed that individuals with at least 1 copy of the OPRM1 + 118 G allele had greater hemodynamic response in mesocorticolimbic areas both before and after priming compared with those who were homozygous for the OPRM1 + 118 A allele. For the DRD4.L and OPRM1 + 118 G groups, brain response in the striatum was highly correlated with measures of alcohol use and behavior such that greater activity corresponded with greater frequency and quantity of alcohol use. Conclusions: The DRD4 VNTR and OPRM1 A118G polymorphisms are associated with functional neural changes in mesocorticolimbic structures after exposure to alcohol cues. This provides evidence for the contributions of the DRD4 and OPRM1 genes in modulating neural activity in structures that are involved in the motivation to drink.

Fillmore MT; Ostling EW; Martin CA; Kelly TH. Acute effects of alcohol on inhibitory control and information processing in high and low sensation-seekers. Drug and Alcohol Dependence 100(1-2): 91-99, 2009. (61 refs.)

Sensation-seeking is a personality characteristic that has been associated with drug abuse. Some evidence suggests that sensation-seekers might experience increased rewarding effects from drugs of abuse, possibly contributing to the association between sensation-seeking and risk for drug abuse. The present study examined the effects of three doses of alcohol (0.0 g/kg, 0.45 g/kg, and 0.65 g/kg) on inhibitory control, information processing, and subjective ratings in a group of high sensation-seekers and a group of low sensation-seekers (N = 20). Inhibitory control was measured by a cued go/no-go task and speed of information processing was assessed by the Rapid Information Processing (RIP) task. Alcohol impaired inhibitory control and information processing. Group differences were also observed. Compared with their low sensation-seeking counterparts, high sensation-seekers demonstrated increased sensitivity to the subjective rewarding effects of alcohol and a poorer degree of inhibitory control that was further impaired by alcohol. The findings highlight reward- and cognitive-based mechanisms by which sensation-seeking could operate to increase risk for alcohol abuse.

Fossos N; Neighbors C; Kaysen D; Hove MC. Intimate partner violence perpetration and problem drinking among college students: The roles of expectancies and subjective evaluations of alcohol aggression. Journal of Studies on Alcohol and Drugs 68(5): 706-713, 2007. (48 refs.)

Objective: The present research examined the effect of alcohol aggression expectancies and subjective evaluations of alcohol's effects on aggression in intimate partner violence (IPV) perpetration among college students. We were interested in determining the extent to which these relationships differed across gender. Method: A total of 780 (57.3% female) incoming heavy drinking college freshmen who were between the ages of 18 and 25 years completed self-reported measures of IPV perpetration, alcohol use and problems, and alcohol aggression expectancies and subjective evaluations of those expectancies as part of the baseline assessment for a larger social norms alcohol intervention study. Analyses evaluated the effect of alcohol aggression expectancies and subjective evaluations of those expectancies on IPV perpetration. Results: Results indicated that problem drinking was positively associated with IPV perpetration for those who were lower (beta=.32, p <.001) versus those who were higher (beta=.07, p = NS) in alcohol aggression expectancies. Among men, there was a significantly stronger relationship between problem drinking and IPV perpetration among those who evaluated alcohol's effects on aggression more favorably (beta=.41, p <.00 1) versus less favorably (beta=. 11, P = NS). Among women, there was not a significantly stronger relationship between problem drinking and IPV perpetration at less favorable (beta=.17, p <.05) versus more favorable (beta= 11, p <.06) evaluations of alcohol's effects on aggression. Conclusions: Findings suggest that, in understanding IPV perpetration, it may not be sufficient to evaluate expected alcohol effects without also including whether those effects are viewed as good or bad. Findings also suggest that the relationship between alcohol problems and IPV perpetration may be stronger and more straightforward for men than for women.

Giancola PR; Corman MD. Alcohol and aggression: A test of the attention-allocation model. Psychological Science 18(7): 649-655, 2007. (33 refs.)

This article presents the first systematic test of the attention-allocation model for alcohol-related aggression. According to this model, alcohol has a "myopic" effect on attentional capacity that presumably facilitates aggression by focusing attention on more salient provocative, rather than less salient inhibitory, cues in hostile situations. Aggression was assessed using a laboratory task in which mild electric shocks were received from, and administered to, a fictitious opponent. Study 1 demonstrated that a moderate-load cognitive distractor suppressed aggression in intoxicated subjects (to levels even lower than those exhibited by a placebo control group). Study 2 assessed how varying the magnitude of a distracting cognitive load affected aggression in the alcohol and placebo conditions. Results indicated that the moderate-load distraction used in Study 1 (i.e., holding four elements in sequential order in working memory) suppressed aggression best. Cognitive loads of larger and smaller magnitudes were not successful in attenuating aggression.

Gilbertson R; Ceballos NA; Prather R; Nixon SJ. Effects of acute alcohol consumption in older and younger adults: Perceived impairment versus psychomotor performance. Journal of Studies on Alcohol and Drugs 70(2): 242-252, 2009. (50 refs.)

Objective: Perceived impairment and psychomotor performance following acute alcohol administration in older (ages 50-74, n = 42; 22 male) and younger (ages 25-35, n = 26; 12 male) adults were investigated in this study. Method: Double-blind, placebo-controlled alcohol administration techniques were designed to produce peak levels of breath alcohol concentration consistent with an episode of social drinking (40 mg/100 ml). Behavioral measures (Trail Making Test, Forms A and B), as well as measures of self-reported perceived intoxication and impairment, were administered on the ascending and descending limbs at common time points after beverage ingestion. Results: Results indicated that psychomotor performance differences did not parallel self-reported levels of perceived impairment. Relative to younger adults, older adults exhibited performance deficits on the ascending limb while simultaneously reporting less perceived impairment. Conversely, on the descending limb, older adults who received alcohol reported more perceived impairment than did those who received placebo, although psychomotor performance between these two groups of older drinkers did not differ. For younger participants, a moderate dose of alcohol facilitated performance on the ascending limb; however, these differences were not reflected on the descending limb. Conclusions: These results reinforce the common knowledge that self-reported measures may not provide an accurate reflection of performance outcomes and, importantly, that older adults may be impaired even under a moderate dose of alcohol, although they may not be aware (i.e., report) of this impairment.

Gilman JM; Hommer DW. Modulation of brain response to emotional images by alcohol cues in alcohol-dependent patients. Addiction Biology 13(3/4): 423-434, 2008. (57 refs.)

Alcohol is often used to modulate mood states. Alcohol drinkers report that they use alcohol both to enhance positive affect and to reduce dysphoria, and alcohol-dependent patients specifically state reduction of negative affect as a primary reason for drinking. The current study proposes that alcohol cues may reduce negative affect in alcoholics. We used functional magnetic resonance imaging to examine brain activation in response to combination images that juxtaposed negative or positive International Affective Picture System (IAPS) images with an alcohol or non-alcohol-containing beverage. We found that in the absence of the alcohol cue, alcoholics showed more activation to negative than to positive images and greater activation than controls to negative images. When the IAPS images were presented with the alcohol cue, there was a decreased difference in activation between the positive and negative images among the alcoholics, and a decreased difference in response to the negative images between controls and alcoholics. Additionally, in the neutral-beverage conditions, anxiety ratings significantly predicted activation in the right parahippocampal gyrus but did not predict activation when the alcohol cues were presented. In conclusion, the alcohol cues may have modulated cortical networks involved in the processing of emotional stimuli by eliciting a conditioned response in the alcoholics, but not in the controls, which may have decreased responsiveness to the negative images.

Gilpin NW; Koob GF. Neurobiology of alcohol dependence focus on motivational mechanisms. Alcohol Research & Health 31(3): 185-195, 2008. (81 refs.)

Alcoholism is a debilitating disorder for the individual and very costly for society. A major goal of alcohol research is to understand the neural underpinnings associated with the transition from alcohol use to alcohol dependence. Positive reinforcement is important in the early stages of alcohol use and abuse. Negative reinforcement can be important early in alcohol use by people self-medicating coexisting affective disorders, but its role likely increases following the transition to dependence. Chronic exposure to alcohol induces changes in neural circuits that control motivational processes, including arousal, reward, and stress. These changes affect systems utilizing the signaling molecules dopamine, opioid peptides, gamma-aminobutyric acid, glutamate, and serotonin, as well as systems modulating the brain's stress response. These neuroadaptations produce changes in sensitivity to alcohol's effects following repeated exposure (i.e., sensitization and tolerance) and a withdrawal state following discontinuation of alcohol use. Chronic alcohol exposure also results in persistent neural deficits, some of which may fully recover following extended periods of abstinence. However, the organism remains susceptible to relapse, even after long periods of abstinence. Recent research focusing on brain arousal, reward, and stress systems is accelerating our understanding of the components of alcohol dependence and contributing to the development of new treatment strategies.

Public Domain

Grattan-Miscio KE; Wickenden M; Crotteau P; Ward A. Examining the myth of the caffeine expectation: Influencing intentional control of behavior under alcohol. International Journal on Disability and Human Development 6(2): 207-214, 2007. (26 refs.)

This experiment was designed to examine the effects of caffeine expectancy on intentional control of behavior under alcohol. Method: A process dissociation paradigm was used to measure the separate influence of automatic and intentional controlled processes on performance of a word-stem completion task. Forty social drinkers studied a list of words, received either alcohol or a placebo, and then performed a word-stem completion task designed to measure intentional control of behavior. Before performing the task, two groups (i.e., one alcohol and one placebo group) also received decaffeinated coffee, which has been shown effectively to establish caffeine expectancy. The results indicated that the expectation of receiving caffeine was sufficient to counteract the impairment of intentional control seen under alcohol. Those individuals who received both alcohol and decaffeinated coffee demonstrated better intentional control than those who received alcohol alone. Moreover, the performance of the alcohol-decaffeinated coffee group did not differ from placebo. No treatment significantly affected automatic processes. Conclusion(s): The expectation of receiving caffeine under alcohol is sufficient to counter-act the impairing effects of the drug.

Happel KI; Rudner X; Quinton LJ; Movassaghi JL; Clark C; Odden AR et al. Acute alcohol intoxication suppresses the pulmonary ELR-negative CXC chemokine response to lipopolysaccharide. Alcohol 41(5): 325-333, 2007. (44 refs.)

Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR+) following lipopolysaccharide (LPS) challenge, but its effect on the structurally related ELR- CXC chemokines, which attract T cells, is unknown. We therefore investigated the effect of acute alcohol intoxication on the pulmonary response to intratracheal (i.t.) LPS challenge for the ELR- CXC chemokines monokine induced by gamma (MIG or CXCL9), interferon-inducible protein 10 (IP-10 or CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11). Male C5713L/6 or C3H/HeN mice were given an intraperitoneal injection of ethanol (3.0 g/kg) or phosphate buffered saline 30 min before i.t. LPS challenge. Chemokine mRNA transcripts were measured at 0, 2, 6, and 16 h. Acute alcohol intoxication inhibited the lung's expression of all three chemokine genes in response to LPS. Lung IFN-gamma mRNA was also inhibited by acute intoxication over the same time course. The in vitro effect of ethanol on chemokine secretion was further studied in the MH-S alveolar macrophage cell line. IP-10, MIG, and I-TAC in response to LPS were enhanced by exogenous interferon (IFN)-gamma, and these responses were blunted by exposure to ethanol. Alcohol exposure did not affect MH-S cell nuclear factor kappa beta p65 nuclear localization during challenge, despite dose-dependent inhibition of Erk 1/2 phosphorylation. In addition, phospho-signal transduction and activator of transcription I was not decreased in the presence of acute ethanol, thereby indicating that acute intoxication does not affect IFN-gamma signaling in MH-S cells. Recruitment of CD3+ T cells into the alveolar space 4 days after LPS challenge was moderately impaired by acute ethanol intoxication. These results implicate acute ethanol intoxication as a significant inhibitor of lymphocyte chemoattractant expression during pulmonary inflammation.

Hernandez OH; Vogel-Sprott M; Ke-Aznar VI. Alcohol impairs the cognitive component of reaction time to an omitted stimulus: A replication and an extension. Journal of Studies on Alcohol and Drugs 68(2): 276-281, 2007. (18 refs.)

Objective: Research from a recent study indicates that cognitive performance is impaired by an acute dose of alcohol at blood alcohol concentrations (BACs) that do not affect motor performance. That study measured reaction time (RT) to the omission of a recurring stimulus and used behavioral criteria to fractionate premotor (cognitive) and motor components of RT when stimuli occurred at slow, 2-second intervals (0.5 Hz). The present experiment tested the generality of the evidence when stimuli occurred at slow or fast, 0. 143 -second intervals (7 Hz). Using muscle potential to fractionate RT, we tested the reproducibility of the findings obtained by a behavioral fractionation procedure. Method: Thirty male social drinkers were randomly assigned to two groups (n = 15 each) that received 0.8 g/kg alcohol or a placebo (0 g/kg). All participants performed a drug-free baseline test and a test during rising BACs. A test presented fast and slow frequency auditory stimuli in counterbalanced order within groups. Results: Tests using both fast and slow frequency stimuli showed that alcohol slowed premotor RT and had no detectable effect on motor RT. Conclusions: Fractionated RT based on muscle potential reproduced the findings based on behavioral fractionation. The generality of the deleterious effects of alcohol on premotor RT was demonstrated by manipulating the frequency of the recurring stimuli. The consistent results obtained with the omitted stimulus paradigm provide a basis for new alcohol research that incorporates electrophysiological measures of the brain potential that are associated with the omission of a stimulus.

Hesse M; Tutenges S. Gender differences in self-reported drinking-induced disinhibition of sexual behaviors. American Journal on Addictions 17(4): 293-297, 2008. (17 refs.)

Sex and drinking go hand-in-hand in Western societies. Men also tend to report more sexual disinhibition under the influence of alcohol and drugs than women. At a vacation resort, we conducted a survey of young men and women regarding self-reported alcohol-related sexual disinhibition (ARSD), and we administered the Drinking-Induced Disinhibition Scale (DIDS). We made several comparisons of behavioral patterns using the ARSD scale of the DIDS for each gender: kissing or having sex vs. no sexual contact, or having sex versus kissing or no contact. In general, men reported more ARSD than women. Men who reported either kissing or having sex the night before reported significantly more ARSD than men not reporting either kissing or having sex. Women who had had sex the night before reported more ARSD than women who had either kissed or not reported any sexual contact on the night before, but women who had kissed did not differ from women who had not had any sexual contact. We suggest that while the DIDS scale of alcohol-related sexual disinhibition is a valid instrument, gender bias exists. In conclusion, the DIDS does measure the constructs that it sets out to measure. However, significant gender differences do exist and appear to go beyond differences in actual behavior in terms of sexual disinhibition. Men and women describe themselves differently when they describe sexual behavior in general, even when they report similar recent behavior, and we suggest that these differences at least partly reflect sexual stereotypes.

Higgs S; Stafford LD; Attwood AS; Walker SC; Terry P. Cues that signal the alcohol content of a beverage and their effectiveness at altering drinking rates in young social drinkers. Alcohol and Alcoholism 43(6): 630-635, 2008. (13 refs.)

Aims: The aim of this study was to assess the impact of cues that signal the alcoholic strength of a beverage on drinking rate in young social drinkers. Methods: In Experiment 1, two groups of young social drinkers (n = 20 per group) consumed a lager-based drink containing either 3% or 7% alcohol-by-volume. The pattern of drinking behaviour was observed, and drinking time was recorded. Self-reported mood was measured across the session, and participants also provided ratings of the drinks' sensory and hedonic properties. Experiment 2 replicated Experiment 1, but used a within-subjects design (n = 12). Results: In both experiments, participants took significantly longer to consume the 7% drink compared with the 3% drink, and the total inter-sip interval was longer for the 7% drink. These effects were most closely related to the participants' changing estimates of alcohol strength across the test session, alongside concomitant changes in various aspects of self-reported mood. Sensory and hedonic evaluations of the drinks did not affect drinking behaviour in either experiment. Conclusions: The findings suggest that the consumption rate of an alcoholic beverage can be modulated by its alcohol content, and that the perceived pharmacological effect of the alcohol serves as an effective signal to alter drinking behaviour.

Hitzemann R; Oberbeck D. Stategies to study the neuroscience of alcoholism: Introduction. (editorial). Alcohol Research & Health 31(3): 231-232, 2008. (0 refs.)

Hutchison KE; Haughey H; Niculescu M; Schacht J; Kaiser A; Stitzel J et al. The incentive salience of alcohol: Translating the effects of genetic variant in CNR1. Archives of General Psychiatry 65(7): 841-850, 2008. (53 refs.)

Context: The gene that codes for cannabinoid receptor 1 (CNR1) represents an important target for investigations designed to elucidate individual differences in the etiology of alcohol dependence. Objective: To achieve a better understanding of the role of the CNR1 gene in the etiology and treatment of alcohol dependence. Design: The present investigation spans multiple levels of analysis, including receptor binding in postmortem brain tissue, neuroimaging, human laboratory models, and analyses of treatment outcome data. Results: Findings indicate that the C allele of rs2023239 is associated with greater CB1 binding in the prefrontal cortex, greater alcohol cue - elicited brain activation in the midbrain and prefrontal cortex, greater subjective reward when consuming alcohol, and more positive outcomes after treatment with a medication that targets the mesocorticolimbic neurocircuitry. In addition, there were strong correlations between cue-elicited brain activation and alcohol consumption measures in individuals with the C allele. Conclusion: Individuals with the C allele may be more susceptible to changes in the mesocorticolimbic neuro-circuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol.

Kawabe H; Saito I; Saruta T. Effects of nighttime alcohol intake on evening and next morning home blood pressure in Japanese normotensives. Clinical and Experimental Hypertension 29(1): 43-49, 2007. (15 refs.)

Home blood pressure (HBP) is usually measured in the morning and evening, but the evening HBP tends to be influenced by an individual's behavior pattern, such as bathing and drinking, which are often seen in the Japanese. In this study, in order to elucidate the influence of nighttime drinking on the evening and next morning HBP and heart rate (HR), HBP measurement was performed in Japanese normotensives under conditions in which the influence of bathing was minimized. Among 700 registered volunteers, 245 normotensives (189 male, 56 female, mean age; 35.8 +/- 0.5 years old) whose data consisted of a combination of drinking and non-drinking on workdays were selected. A semi-automatic device was lent to all participants, and they were asked to perform triplicate morning and evening measurements on seven consecutive days between October 16, 2002, and November 13, 2002. The differences in evening HBP and HR between the drinking and non-drinking days were calculated, as were the differences in the next morning HBP and HR. Only data of evening HBP measured at least 30 min after bathing were accepted. Evening SBP and DBP on drinking days were significantly lower (2.5 +/- 0.5 mmHg, 3.1 +/- 0.5 mmHg) than those on non-drinking days. On the other hand, evening HR on drinking days was significantly higher (7.7 +/- 0.8 b.p.m.) than that on non-drinking days. Although there was no difference in morning SBP after days with and without drinking, morning DBP the day after drinking was slightly (0.8 +/- 0.3 mmHg) but significantly lower than that the day after non-drinking. Morning HR the day after drinking was significantly higher (2.4 +/- 0.4 b.p.m.) than that after non-drinking. Because nighttime drinking influenced the evening HBP even in normotensives, it was suggested that morning HBP could give more stable values than evening HBP in Japanese people.

Khan SA; Timney B. Alcohol does not affect dark adaptation or luminance increment thresholds. Journal of Studies on Alcohol and Drugs 68(4): 493-502, 2007. (32 refs.)

Objective: It has been proposed that alcohol might induce within the retina a state akin to dark adaptation. However, the evidence to support this proposal is quite indirect. Another possibility is that alcohol might affect retinal gain control rather than sensitivity. To investigate these proposals psychophysically, we measured dark adaptation functions and increment thresholds with the increment threshold procedure in individuals with moderate blood alcohol concentrations (BACs). Method: Individuals were tested under both alcohol and no-alcohol conditions (BAC approximate to.08%). In Experiment 1, thresholds for the detection of a parafoveal target were measured over a 25-minute period following a 3-minute bleach in six males. In Experiment 2, the cone dark adaptation function of four males was examined in more detail for a foveal target following bleaching at three different levels. In Experiment 3, we measured the thresholds of nine men for a small target superimposed on a background field that varied over 4 log units in luminance. Results: We found no effects of alcohol on either the rod or the cone portion of the dark adaptation curve or on increment thresholds. Conclusions: Together, these data indicate that moderate alcohol ingestion does not affect the recovery of visual sensitivity in the dark nor does it affect gain control at the retinal level.

Kim SH; Abbasi F; Lamendola C; Reaven GM. Effect of moderate alcoholic beverage consumption on insulin sensitivity in insulin-resistant, nondiabetic individuals. Metabolism: Clinical and Experimental 58(3): 387-392, 2009. (31 refs.)

Although moderate alcohol consumption has been associated with a decrease in plasma insulin concentrations, relatively few studies have been conducted to evaluate the effect of alcohol on insulin sensitivity, particularly in nondiabetic, insulin-resistant individuals. Because enhanced insulin sensitivity could contribute to the reported association between moderate alcohol consumption and reduced risk of heart disease and diabetes, we believed it is important to address this issue. Consequently, we evaluated the ability of moderate alcohol consumption to improve insulin sensitivity, as measured by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, in 20 nondiabetic, insulin-resistant individuals. Measurements were made of SSPG, glucose, insulin, and lipoprotein concentrations before and after consuming 30 g of alcohol for 8 weeks, either as vodka (n = 9) or red wine (n = 11). The SSPG concentrations (insulin resistance) decreased by approximately 8% in the total group (P = .08), and high-density lipoprotein cholesterol concentration increased by a mean of 0.09 mmol/L (P = .02). Trends were similar in individuals who consumed vodka or red wine. Men tended to have greater decline in SSPG and increase in high-density lipoprotein cholesterol compared with women. There were no other metabolic changes in fasting plasma glucose, insulin, and triglyceride concentrations. These data demonstrate that 8 weeks of moderate alcohol consumption had minimal impact on enhancing insulin sensitivity in nondiabetic, insulin-resistant individuals, raising questions as to the role, if any, of improved insulin sensitivity in the purported clinical benefits associated with moderate alcohol consumption.

Kingree JB; Thompson M. Sexually-related expectancies for alcohol use and marijuana use among juvenile detainees. Addictive Behaviors 32(9): 1936-1942, 2007. (10 refs.)

This study is focused on sexually-related expectancies for substance use among juvenile detainees. Over a 6 month period, 272 juveniles recruited from a short-term detention facility completed measures assessing sexually-related expectancies in relation to alcohol use and marijuana use as well as measures assessing their actual use of these substances. Repeated measures analyses of sexual risk expectancy measures indicated that the sample as a whole, and older respondents in particular, expected more sexual risk in relation to using alcohol than in relation to using marijuana. Repeated measures analyses of sexual enhancement expectancy measures indicated that Aftican-American and younger respondents expected more sexual enhancement from using marijuana than from using alcohol. Logistic regression analyses indicated that expectancies for sexual enhancement from alcohol use, and expectancies for sexual enhancement from marijuana use, were respectively associated with the use of these substances in a recent sexual incident. Limitations of the study are discussed.

Kream RM; Stefano GB. Homeopathic ethanol. Medical Science Monitor 14(9): SC11-SC13, 2008. (42 refs.)

Ethanol has had a long and deep association with the historical development of world culture. Ostensibly, its consumption has both short and long term positive and negative effects, based on moderate or excessive intake, respectively. The predominant thrust of empirical research, however, into the multiple biological effects of ethanol has led to its negative designation as a major addictive substance. Multiple lines of research have elucidated functional interactions of ethanol in opioid modulation of dopaminergic transmission in CNS reward systems. Parallel, recent work has demonstrated that animal cells have the ability to effect de novo synthesis of chemically authentic morphine from dopamine (DA) and DA-related aromatic precursor molecules. Interestingly, we have observed that sub-threshold concentrations of ethanol alter cellular distributions of endogenously expressed morphine. Reciprocal autocrine/paracrine modulatory effects, low concentrations of morphine in concert with ethanol also suggest the potential for endogenous expression and action of homeopathic concentrations of ethanol within discrete cellular microdomains. Perturbation of this subtle regulatory relationship by exogenous intake of ethanol may shed light on the biochemical and molecular bases of reward and addictive states.

Labrie JW; Hummer JF; Pedersen ER. Reasons for drinking in the college student context: The differential role and risk of the social motivator. Journal of Studies on Alcohol and Drugs 68(3): 393-398, 2007. (42 refs.)

Objective: The present study examines the relationships among reasons for drinking, alcohol consumption, and alcohol-related consequences in two college-aged samples. Personal motivators such as mood enhancement and coping (tension reduction) have consistently been shown to predict problematic alcohol use, but because of the salient nature of social drinking in college, we hypothesized that social reasons for drinking would be most frequently endorsed and, in turn, predict negative consequences. Method: Two distinct samples --19 co-ed adjudicated students sanctioned by the university for violating campus alcohol policy and 106 co-ed volunteer students -- completed measures assessing alcohol consumption, reasons for drinking, and consequences. Differential effects between genders were examined. Results: Social camaraderie (SC) was the most frequently endorsed reason for drinking. Regression analyses controlling for previous drinking revealed that social reasons for drinking predicted alcohol-related problems among female students in both samples. Additionally, SC was significantly correlated with every drinking measure and problem measure at 1 month for females in both the adjudicated and the volunteer groups. Total drinks, drinking days, and heavy episodic drinking events correlated with SC for males in the adjudicated sample. Conclusions: For females, these results suggest a relationship between social reasons for drinking and alcohol-related consequences, which previous research has not identified. More research is needed to explore females' reasons for drinking, accompanying problems, and the underlying psychosocial traits associated with these reasons.

Lange RT; Iverson GL; Franzen MD. Short-term neuropsychological outcome following uncomplicated mild TBI: Effects of day-of-injury intoxication and pre-injury alcohol abuse. Neuropsychology 21(5): 590-598, 2007. (67 refs.)

Research suggests that individuals who are intoxicated at the time of traumatic brain injury (TBI) have worse cognitive outcome compared with those who are sober. Worse outcome in patients with day-of-injury intoxication might (a) be related to the increased magnitude of brain injury resulting from a variety of negative responses not present following TBI in nonintoxicated individuals, or (b) reflect the effect of pre-injury alcohol abuse that is prevalent in individuals intoxicated at the time of injury. Most studies in this area have focused on patients with moderate to severe TBIs, and on medium- to long-term neuropsychological outcome. The purpose of this study was to examine the relative contributions of day-of-injury intoxication versus pre-injury alcohol abuse on short-term cognitive recovery following mild TBI. Participants were 169 patients with uncomplicated mild TBIs who were assessed on 13 cognitive measures within 7 days postinjury. The prevalence of intoxication at the time of injury was 54.4%. The prevalence of possible pre-injury alcohol abuse was 46.2%. Overall, the results suggest that pre-injury alcohol abuse, compared with day-of-injury alcohol intoxication, had the most influence on short-term neuropsychological outcome from uncomplicated mild TBI. However, the influence of pre-injury alcohol abuse was considered small at best.

Leeman RF; Toll BA; Volpicelli JR. The Drinking-Induced Disinhibition Scale (DIDS): A measure of three types of disinhibiting effects. Addictive Behaviors 32(6): 1200-1219, 2007. (41 refs.)

Links between trait disinhibition and high-risk drinking are well established. It is also known that alcohol has disinhibiting effects. Nonetheless, there is no measure in the literature devoted exclusively to assessing disinhibiting effects of alcohol. The multidimensional Drinking-Induced Disinhibition Scale (DIDS) was developed as part of Study 1, a prospective survey conducted with undergraduates (N=337). Study 11, a cross-sectional survey (N = 260), allowed for a confirmatory factor analysis and further validation of the measure through comparisons with an expectancies scale. The nine-item DIDS is comprised of three subscales assessing euphoric/social, dysphoric and sexual disinhibition. All three subscales had good internal consistency and adequate test-retest reliability. Convergent and discriminant validity were established in both studies. The subscales had different associations with high-risk drinking: sexual disinhibition predicted heavy episodic drinking; dysphoric disinhibition predicted alcohol-related problems and euphoric/social had associations with both. A cluster analysis revealed four distinct disinhibition profiles (i.e., low effect drinker; high euphoric/social only; high euphoric social and dysphoric; high euphoric/social and sexual), which predicted likelihood of high-risk drinking.

Li CSR; Luo X; Yan P; Bergquist K; Sinha R. Altered impulse control in alcohol dependence: Neural measures of stop signal performance. Alcoholism: Clinical and Experimental Research 33(4): 740-750, 2009. (99 refs.)

Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence. To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial-by-trial evaluation of response inhibition, error processing, and post-error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance. The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post-error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post-error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk-taking decisions in the SST. These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.

Lind PA; MacGregor S; Montgomery GW; Heath AC; Martin NG; Whitfield JB. Effects of GABRA2 variation on physiological, psychomotor and subjective responses in the alcohol challenge twin study. Twin Research and Human Genetics 11(2): 174-182, 2008. (24 refs.)

Multiple reports have identified variation in the GABRA2 gene as contributing to the genetic susceptibility to alcohol dependence. However, both the mechanism behind this association, and the range of alcohol-related phenotypes affected by variation in this gene, are currently undefined. Other data suggest that the risk of alcohol dependence is increased by relative insensitivity to alcohol's intoxicating effects. We have therefore tested whether GABRA2 variation is associated with variation in the subjective and objective effects of a standard dose of alcohol in humans. Data on responses to alcohol from the Alcohol Challenge Twin Study (Martin et al., 1985) have been tested against allelic and haplotype information obtained by typing 41 single-nucleotide polymorphisms in or close to the GABRA2 gene. Nominally significant allelic associations (p < .05, without correction for multiple testing) were found for body sway, motor coordination, pursuit rotor and arithmetical computation tasks, and for the personality dimension of Neuroticism. Because of the large number of phenotypes tested, these possibly significant findings will need to be confirmed in further studies.

Lovinger DM. Communication networks in the brain neurons, receptors, neurotransmitters, and alcohol. (review). Alcohol Research & Health 31(3): 196-214, 2008. (141 refs.)

Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neuro transmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neuro transmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones, This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

Public Domain

Marczinski CA; Harrison ELR; Fillmore MT. Effects of alcohol on simulated driving and perceived driving impairment in binge drinkers. Alcoholism: Clinical and Experimental Research 32(7): 1329-1337, 2008. (57 refs.)

Background: Binge drinking (heavy episodic alcohol use) is associated with high rates of impaired driving and myriad alcohol-related accidents. However, the underlying reasons for the heightened accident risk in this demographic group are not known. This research examined acute alcohol effects on simulated driving performance and subjective ratings of intoxication and driving ability in binge and nonbinge drinkers. Methods: Young social drinking college students (24 binge drinkers and 16 nonbinge drinkers) participated in this study. Participants attended a session during which they received a moderate dose of alcohol (0.65 g/kg) and a session during which they received a placebo. A simulated driving task measured participants' driving performance in response to each dose. Subjective responses to each dose were also assessed, including ratings of sedation, stimulation, and driving ability. Results: The acute dose of alcohol impaired multiple aspects of driving performance in both binge and nonbinge drinkers. Under alcohol, all participants had greater difficulty in maintaining their lane position, maintaining the appropriate speed and made multiple driving errors compared to placebo performance. By contrast, compared with nonbinge drinkers, binge drinkers reported feeling less sedated by the alcohol and reported having a greater ability to drive following the acute dose of alcohol. Conclusion: Reduced subjective intoxication and perceived driving impairment in binge drinkers may account for the greater accident risk in this demographic group. Binge drinkers may lack the internal sedation cue that helps them accurately assess that they are not able to effectively drive a vehicle after drinking.

Mills KC; Spruill SE; Walker JM; Lamson M. A clinical trial demonstration of a web-based test for alcohol and drug effects. Journal of Studies on Alcohol and Drugs 70(2): 308-313, 2009. (12 refs.)

Objective: The purpose of this study was to determine the feasibility of a Web-installed test of skills essential to driving: target detection and divided attention. The Attention Assessment (TAA) was designed for use in global clinical trials to document the effects of alcohol and other drugs. Method: Scoring algorithms and data-storage tools were installed on servers in bicoastal U.S. locations. IBM PC-compatible test units with encrypted Web access and 19-inch monitors were installed at a Canadian site. A single-center, crossover design was used to compare the pharmacodynamic properties of a pharmaceutical compound under development with those of alcohol (blood alcohol concentration [BAC] = .10%) over time. For this study, 33 subjects completed four 36-hour testing periods. Blood samples and pharmacodynamic assessments were performed at 0, 1, 3, 5, 7 9, 12, and 24 hours. Analysis of covariance was conducted on six composite TAA scores as change from baseline. Results: Five of the six composite scores showed significant ethanol effects (p < .02) over a BAC range of .1% to .05%. Within-session test-retest reliability was r = .86 and between periods was r = .51 (between Periods 1 and 2), .83 (between Periods 2 and 3), and .81 (between Periods 3 and 4). Individual impairment was evident at .05%. Conclusions: It was possible to conduct sensitive alcohol/other drug testing from a central database with secure scoring. Test installation, data monitoring, and norms assembly were performed at a remote location. TAA gives researchers the ability to immediately and normatively evaluate alcohol and drug effects in diverse global locations. Secondary applications include clinical or worksite testing. The data show improved precision over previous test versions to map the effect of drugs on visual/cognitive skills involved in driving.

Monahan JL; Samp JA. Alcohol's effects on goal-related appraisals and communicative behaviors. Communication Research 34(3): 332-351, 2007. (51 refs.)

Guided by research demonstrating that intoxication impairs cognitive processing, this study examined the effects of drinking on goal-related appraisals and communication behavior during cooperative interactions. In it, 42 male teams played four rounds of a cooperative game whereby one person produced clues and the other guessed the category the clues described. One partner was sober and the other was randomly assigned to drinking condition (sober or breath alcohol count of.08 g/dl). Analyses compared the appraisals and behaviors of the participant randomly assigned to drinking condition. Intoxicated participants felt less anxious and judged games as less challenging yet did not feel they had more control compared to their sober counterparts. Behaviorally, intoxicated participants exhibited more persistence yet were less flexible in goal pursuit than were sober participants. Ultimately, intoxicated-sober dyads had more success than did sober-sober dyads. Implications for message production under the influence of alcohol are discussed.

Morean ME; Corbin WR. Subjective alcohol effects and drinking behavior: The relative influence of early response and acquired tolerance. Addictive Behaviors 33(10): 1306-1313, 2008. (32 refs.)

Objectives: (1) To establish the reliability and validity of a modified version of the Self-Rating of Alcohol (SRE) form. (2) To differentiate early subjective alcohol response (SR) from acquired tolerance in the prediction of drinking outcomes. Method: 353 undergraduates completed an online survey. SR was assessed using the SIZE form and a modified SRE including items assessing global stimulant and sedative effects. The Daily Drinking Questionnaire-Revised (DDQ-R), and the Rutgers Alcohol Problems Index (RAPI) assessed alcohol use and problems, respectively. Results: The revised version of the SRE showed good internal consistency and incremental validity. Early SR assessed by the modified SIZE was consistently associated with use and problems. Acquired tolerance was significantly related to use and problems above and beyond early SR. Conclusions: The modified SIZE incorporating stimulant and sedative responses demonstrated good psychometric properties and the potential to capture unique variability in drinking outcomes. Differentiating early SR from tolerance showed that each contributes uniquely to drinking behavior and problems. Thus, future studies would benefit from examining the unique contribution of each aspect of SR.

Neave N; Tsang C; Heather N. Effects of alcohol and alcohol expectancy on perceptions of opposite-sex facial attractiveness in university students. Addiction Research & Theory 16(4): 359-368, 2008. (21 refs.)

Previous research has indicated that alcohol consumption increases the perceived attractiveness of opposite-sex faces. This may contribute to the known effects of alcohol on risky sexual behaviours. We investigated the effects of alcohol consumption on the perception of opposite-sex faces, whilst controlling for alcohol expectancy. In a balanced placebo design, males and females were allocated to one of the four groups: (1) told they would receive alcohol and did; (2) told they would receive alcohol but did not; (3) told they would not receive alcohol but did; (4) told they would not receive alcohol and did not. They then rated opposite-sex faces and neutral stimuli for 'attractiveness'. Roughly three-quarters of the sample were classified as hazardous or harmful drinkers by the AUDIT questionnaire. No significant differences between groups in ratings of attractiveness for either set of stimuli were found. Findings remained the same in a reduced sample for whom the experimental manipulation was successful (as assessed by post-test questioning). Thus, we did not find that alcohol ingestion enhanced ratings of opposite-sex faces. Nor did we find that, in the overall sample, the expectation of receiving an alcoholic drink influenced opposite-sex face ratings. Possible explanations for these null findings are discussed.

Onaivi ES. An endocannabinoid hypothesis of drug reward and drug addiction. Annals of the the New York Academy of Sciences. Drug Addiction: Research Frontiers and and Treatment Advances 1139: 412-421, 2008. (23 refs.)

Pharmacologic treatment of drug and alcohol dependency has largely been disappointing, and new therapeutic targets and hypotheses are needed. There is accumulating evidence indicating a central role for the previously unknown but ubiquitous endocannabinoid physiological control system (EPOS) in the regulation of the rewarding effects of abused substances. Thus an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and are involved in the regulation of synaptic transmission to suppress neurotransmitter release by the presynaptic cannabinoid receptors (CB-Rs). This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Our data, along with those from other investigators, provide strong new evidence for a role for EPOS modulation in the effects of drugs of abuse, and specifically for involvement of cannabinoid receptors in the neural basis of addiction. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs. The results suggest that the EPOS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.

Osborne MPH; Olive MF. A role for mGluR5 receptors in intravenous methamphetamine self-administration. Annals of the the New York Academy of Sciences. Drug Addiction: Research Frontiers and and Treatment Advances 1139: 206-211, 2008. (32 refs.)

Selective antagonists of the mGluR5 receptor attenuate rewarding and reinforcing effects of various drugs of abuse, including alcohol, nicotine, and cocaine. However, the ability of mGluR5 antagonists to alter the reinforcing effects of methamphetamine has not yet been explored. In this study, male Sprague-Dawley rats were trained to perform an operant lever-pressing task in order to obtain intravenous infusions of methamphetamine (0.2 mg/kg/infusion) or presentation of food pellets on a fixed ratio (FR1) schedule of reinforcement. After stabilization of methamphetamine or food self-administration, the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]pyridine (MTEP; 0.3, 1.0, or 3.0 mg/kg i.p.) or vehicle were administered to the animals in a randomized counterbalanced cross-over design. MTEP at doses of 1.0 and 3.0 mg/kg significantly reduced methamphetamine self-administration by 26 and 36%, respectively, but did not alter food reinforcement at any dose tested. These data suggest that mGluR5 receptors are involved in the reinforcing effects of methamphetamine, and that antagonists of this receptor may serve as novel pharmacologic agents for the treatment of addiction to methamphetamine.

Parker LLC; Penton-Voak IS; Attwood AS; Munafo MR. Effects of acute alcohol consumption on ratings of attractiveness of facial stimuli: Evidence of long-term encoding. Alcohol and Alcoholism 43(6): 636-640, 2008. (20 refs.)

Aim: A strongly held popular belief is that alcohol increases the perceived attractiveness of members of the opposite sex. Despite this, there are no experimental data that investigate this possibility. We therefore explored the relationship between acute alcohol consumption and ratings of attractiveness of facial stimuli. Methods: We investigated male and female participants (n = 84), using male and female facial stimuli, in order to investigate possible sex differences, and whether any effects of alcohol are selective for opposite-sex facial stimuli. We tested participants immediately following consumption of alcohol or placebo and one day later, in order to investigate whether any effects of alcohol persist beyond acute effects. Results: Attractiveness ratings were higher in the alcohol compared to the placebo group (F[1, 80] = 4.35, P = 0.040), but there was no evidence that this differed between males and females or was selective for opposite-sex faces. We did not observe marked effects of alcohol on self-reported measures of mood, suggesting that the effects on ratings of attractiveness were not due simply to global hedonic effects or reporting biases. Conclusions: Alcohol consumption increases ratings of attractiveness of facial stimuli, and this effect is not selective for opposite-sex faces. In addition, the effects of alcohol consumption on ratings of attractiveness persist for up to 24 h after consumption, but only in male participants when rating female (i.e. opposite-sex) faces.

Patrick KS; Straughn AB; Minhinnett RR; Yeatts SD; Herrin AE; DeVane CL et al. Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics. Clinical Pharmacology & Therapeutics 81(3): 346-353, 2007. (31 refs.)

This study explores the hypotheses that: (1) ethanol will interact with di-Methylphenidate (MPH) to enantioselectively elevate plasma d-MPH, and primarily yield l-ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex-dependent differences in subjective effects will exist. dI-MPH HCl (0.3 mg/kg) was administered orally 30 min before ethanol, 30 min after ethanol (0.6 gm/kg), or without ethanol, in a randomized, normal subject three-way crossover study of 10 men and 10 women. Pharmacokinetic parameters were compared. Subjective effects were recorded using visual analog scales. One subject was a novel poor MPH metabolizer whose data were analyzed separately. Ethanol after or before MPH significantly (P < 0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration (C-max (+/- SD)) from 15.3 (3.37) ng/ml to 21.5 (6.81) and 21.4 (4.86), respectively, and raised the corresponding geometric mean for the area under the concentration-time curve values from 82.9 (21.7) ng ml/h to 105.2 (23.5) and 102.9 (19.2). I-MPH was present in plasma only at 1-3% of the concentration of d-MPH, except in the poor metabolizer where I-MPH exceeded that of d-MPH. The metabolite l-ethylphenidate frequently exceeded 1 ng/ml in plasma, whereas d-ethylphenidate was detected only in low pg/ml concentrations. Women reported a significantly greater stimulant effect than men when questioned "Do you feel any drug effect?" (P < 0.05), in spite of lower mean plasma d-MPH area under the response-time curves in women. Ethanol elevates plasma d-MPH C-max and area under the concentration-time curve by approximately 40% and 25%, respectively. If the poor metabolizer of MPH proves to be a distinct phenotype, determining the genetic mechanism may be of value for individualizing drug therapy. The more pronounced stimulant effects experienced by women have sex-based abuse liability implications.

Pedersen SL; McCarthy DM. An examination of subjective response to alcohol in African Americans. Journal of Studies on Alcohol and Drugs 70(2): 288-295, 2009. (38 refs.)

Objective: Alcohol response is a widely studied risk factor for heavy drinking behavior and alcohol-use disorders. This study examined acute subjective response to alcohol as a predictor of drinking behavior, alcohol-related problems, and family history of alcoholism in African Americans. The convergent validity of self-reported response to alcohol (Self-Rating of the Effects of Alcohol scale [SRE]) in an African-American sample was also examined. Method: One hundred and three African-American young adults participated in an alcohol-challenge study, receiving a moderate dose of alcohol (0.72 g/kg alcohol for men, 0.65 g/kg for women). Breath alcohol concentration and subjective response to alcohol were assessed before beverage consumption, in 15-minute intervals for the first hour following consumption, and in 30-minute intervals thereafter. Results: Latent variable growth models indicated that experiencing increased acute stimulation from alcohol was related to past-month drinking behavior and alcohol-related problems. Regression analyses indicated that the SRE was related to drinking behavior, alcohol-related problems, having an alcohol-use disorder, and a family history of alcoholism. The SRE was not related to either sedation or stimulation following alcohol administration. Conclusions: Results support alcohol response as a marker of risk for increased drinking behavior and alcohol-related problems in African Americans. Further research is required to directly compare African-American and white response to alcohol within an alcohol-challenge paradigm.

Pepino MY; Steinmeyer AL; Mennella JA. Lactational state modifies alcohol pharmacokinetics in women. Alcoholism: Clinical and Experimental Research 31(6): 909-918, 2007. (62 refs.)

Background: Given the physiological adaptations of the digestive system during lactation, the present study tested the hypothesis that lactation alters alcohol pharmacokinetics. Methods: Lactating women who were exclusively breastfeeding a 2- to 5-month-old infant and 2 control groups of nonlactating women were studied. The first control group consisted of women who were exclusively formula-feeding similarly aged infants, whereas the other consisted of women who had never given birth. A within-subjects design study was conducted such that women drank a 0.4 g/kg dose of alcohol following a 12-hour overnight fast during one test session (fasted condition) or 60 minutes after consuming a standard breakfast during the other (fed condition). Blood alcohol concentration (BAC) levels and mood states were obtained at fixed intervals before and after alcohol consumption. Results: Under both conditions, the resultant BAC levels at each time point were significantly lower and the area under the blood alcohol time curve were significantly smaller in lactating women when compared with the 2 groups of nonlactating women. That such changes were due to lactation per se and not due to recent parturient events was suggested by the finding that alcohol pharmacokinetics of nonlactating mothers, who were tested at a similar time postpartum, were no different from women who had never given birth. Despite lower BAC levels in lactating mothers, there were no significant differences among the 3 groups of women in the stimulant effects of alcohol. However, lactating women did differ in the sedative effects of alcohol when compared with nulliparous but not formula-feeding mothers. That is, both groups of parous women felt sedated for shorter periods of time when compared with nulliparous women. Conclusions: The systemic availability of alcohol was diminished during lactation. However, the reduced availability of alcohol in lactating women did not result in corresponding changes in the subjective effects of alcohol.

Perrino AC; Ralevski E; Acampora G; Edgecombe J; Limoncelli D; Petrakis IL. Ethanol and pain sensitivity: Effects in healthy subjects using an acute pain paradigm. Alcoholism: Clinical and Experimental Research 32(6): 952-958, 2008. (33 refs.)

Background: The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration-dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that a positive family history for alcoholism individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN). Methods: Forty-one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady-state ("clamp") ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60-min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11-point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states. Results: Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (-2.4, -1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses. Conclusion: The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol's analgesic effects.

Pian JP; Criado JR; Ehlers CL. Differential effects of acute alcohol on prepulse inhibition and event-related potentials in adolescent and adult Wistar rats. Alcoholism: Clinical and Experimental Research 32(12): 2062-2073, 2008. (90 refs.)

Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram. However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse + pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. These data suggest that alcohol's effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol-influenced response to PPI.

Piasecki TM; McCarthy DE; Fiore MC; Baker TB. Alcohol consumption, smoking urge, and the reinforcing effects of cigarettes: An ecological study. Psychology of Addictive Behaviors 22(2): 230-239, 2008. (56 refs.)

Smokers (N = 74) who volunteered for a smoking cessation study monitored their daily experiences for up to 6 weeks prior to the quit date. Self-reports from 7,707 diary records were used to examine the associations among alcohol consumption (present in 607 diary records), situational factors, smoking, urge to smoke, and subjective consequences of smoking. Alcohol use, smoking urge, and the subjective effects of smoking were context dependent. Momentary reports of smoking and alcohol consumption were associated with one another. Alcohol use predicted smoking even when contextual factors were covaried. Alcohol use was associated with more frequent reports of urge to smoke. Alcohol was also associated with more frequent reports that the last cigarette produced a rush/buzz, was good tasting, and reduced the urge. However, effects for rush/buzz and urge reduction were qualified by interactions between alcohol use and the latency since smoking. Rush/buzz tended to be associated with alcohol use, regardless of smoking recency. Alcohol was associated with urge reduction only when the cigarette being appraised was smoked more than 15 minutes prior to the diary entry.

Ramchandani VA; Plawecki M; Li TK; O'Connor S. Intravenous ethanol infusions can mimic the time course of breath alcohol concentrations following oral alcohol administration in healthy volunteers. Alcoholism: Clinical and Experimental Research 33(5): 938-944, 2009. (27 refs.)

Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (C-max), times of peak BrAC (T-max), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean C-max, T-max, and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC-time courses, on average, for females and males. The IV infusion driven BrAC-time profiles demonstrated good fidelity to the BrAC-time curves resulting from oral alcohol: the mean %difference in C-max and AUC were both 11%, while the mean %difference for T-max was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response.

Ray LA; Hutchison KE; MacKillop J; Miranda R; Audette A; Swift R et al. Effects of naltrexone during the descending limb of the blood alcohol curve. American Journal on Addictions 17(4): 257-264, 2008. (72 refs.)

The neuropharmacological effects of alcohol are known to vary by limb of the blood alcohol curve, yet human laboratory studies of alcoholism pharmacotherapies have largely failed to consider limb of intoxication when examining medication effects on subjective responses to alcohol. This study examined the effects of naltrexone compared to placebo on subjective responses to alcohol at the descending limb of the blood alcohol curve following a controlled intravenous (IV) alcohol administration. Non-treatment-seeking hazardous drinkers (n = 38) completed two double-blind counterbalanced IV alcohol challenge sessions, one after taking naltrexone (50 mg) for three days and one after taking a placebo for three days. During each session, participants reported on subjective responses to alcohol during the descending limb of the blood alcohol curve. Analyses revealed significant main effects of naltrexone, reflecting significantly decreased alcohol-induced stimulation, craving, vigor, positive mood, and alcohol high and increased tension as compared to placebo. These findings suggest that naltrexone may exert some of its therapeutic effects via alterations to experiential aspects of intoxication during the descending limb of alcohol intoxication. Additionally, these results highlight the potential utility of considering limb of blood alcohol curve when examining the mechanisms of action of pharmacotherapies thought to alter subjective responses to alcohol.

Richardson HN; Lee SY; O'Dell LE; Koob GF; Rivier CL. Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state. European Journal of Neuroscience 28(8): 1641-1653, 2008. (77 refs.)

Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in 'low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging similar to 0.4 mg/kg/session), and most blunted in dependent animals (averaging similar to 1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.

Riley SCE; Blackman G. Between prohibitions: Patterns and meanings of magic mushroom use in the UK. Substance Use & Misuse 43(1): 55-71, 2008. (29 refs.)

A survey of magic mushroom use was completed by 174 participants in 2004, a year when the sale of hallucinogenic mushrooms was not illegal in the UK. The data were collected in Edinburgh and Bristol (UK). Participants were a self-selecting convenience sample. Participants tended to be in their 20s, White-British, in education or employed; 64% were male. Participants reported a pattern of infrequent but intense consumption (47% used between 4-12 times/year, average consumption in one setting was 12 g, a high dose). Use was explained in terms of laughing, hallucinations, altering perspective (41-74%), and feelings of being closer to nature (49%). Negative experiences reported included paranoia (35%) and anxiety (32%). Mushroom use was located within a wider recreational drug and alcohol culture. Four focus groups aided the interpretation of the data. Future research is recommended into negative experiences. Implications for policy and harm minimisation literature are discussed.

Ronen A; Gershon P; Drobiner H; Rabinovich A; Bar-Hamburger R; Mechoulam R et al. Effects of THC on driving performance, physiological state and subjective feelings relative to alcohol. Accident Analysis and Prevention 40(3): 926-934, 2008. (28 refs.)

Background: The effects of marijuana or THC on driving has been tested in several studies, but usually not in conjunction with physiological and subjective responses and not in comparison to alcohol effects on all three types of measures. Objective: To assess the effects of two dosages of THC relative to alcohol on driving performance, physiological strain, and subjective feelings. Method: We tested the subjective feelings and driving abilities after placebo, smoking two dosages of THC (13 mg and 17 mg), drinking (0.05% BAC) and 24 h after smoking the high dose THC cigarette, while monitoring physiological activity of the drugs by heart rate. Fourteen healthy students, all recreational marijuana users, participated in the study. Results: Both levels of THC cigarettes significantly affected the subjects in a dose-dependent manner. The moderate dose of alcohol and the low THC dose were equally detrimental to some of the driving abilities, with some differences between the two drugs. THC primarily caused elevation in physical effort and physical discomfort during the drive while alcohol tended to affect sleepiness level. After THC administration, subjects drove significantly slower than in the control condition, while after alcohol ingestion, subjects drove significantly faster than in the control condition. No THC effects were observed after 24 h on any of the measures.

Rose AK; Duka T. The influence of alcohol on basic motoric and cognitive disinhibition. Alcohol and Alcoholism 42(6): 544-551, 2007. (30 refs.)

It has been proposed that alcohol weakens control processes, which in turn supports the occurrence of disinhibited behaviours. Two studies were run, in parallel (both with 32 participants) using a between-subject design to investigate any disinhibiting effects of a moderate dose of alcohol (0.6 g/kg compared to placebo), previously found to trigger increased desire for alcohol. Disinhibiting effects were tested on basic motoric and cognitive control processes, using a go/no-go (GNG) and the Stroop task (ST) respectively. Although a higher proportion of participants wanted more alcohol under the alcohol preload (priming effect), this effect was not found to be significant. In the GNG task, correct response latency (RL) decreased from baseline [P=0.008] while number of incorrect hits increased [P=0.030] irrespective of treatment, indicating the formation of a habit-like response and motoric disinhibition. Although error rate did not differ between groups, an interaction occurred with regard to erroneous RL: participants under alcohol became quicker, while those under placebo became slower [P=0.014]. In the ST, those preloaded with alcohol made significantly more errors [P=0.021] and were quicker to complete the task [P=0.044] compared with those preloaded with placebo, indicating a strong alcohol effect on cognitive disinhibition. The data suggest that a moderate dose of alcohol, which induces priming to want more alcohol, had disinhibiting effects both on a basic motoric and a cognitive inhibitory task. Thus the idea that priming may be mediated by the disinhibitory effects of alcohol is supported.

Rose AK; Grunsell L. The subjective, rather than the disinhibiting, effects of alcohol are related to binge drinking. Alcoholism: Clinical and Experimental Research 32(6): 1096-1104, 2008. (59 refs.)

Background: Evidence suggests that alcohol-related problems are associated with impulsivity and disinhibited behavior. Less certain is whether disinhibited behavior is due to an impulsive disposition or alcohol's ability to disinhibit some people more than others. There are a range of disinhibited behaviors associated with alcohol, including excessive alcohol consumption, bingeing. The study tested whether nondependent alcohol bingers showed more disinhibition after placebo and/or alcohol relative to nonbingers and whether this was related to enhanced motivation to drink following a priming dose of alcohol. Methods: Twenty participants (10 bingers) attended the laboratory twice. Baseline measures included impulsivity, alcohol-related cognitions, alcohol urge, and mood. Participants were preloaded with alcohol (male: 0.6 g/kg, female: 0.5 g/kg) and placebo (counterbalanced). After a 20-minute rest, participants completed 2 impulsivity tasks (Two Choice & Time Estimation) separated by second urge and mood ratings. Results: Bingers did not show greater impulsivity characteristics but were more concerned about their drinking (p = 0.02) and ability to control drinking (p = 0.04). A priming effect was found: alcohol urge increased after alcohol but not placebo (p = 0.006). Bingers reported greater tolerance to the sedative (p = 0.05) and lightheaded (p = 0.04) effects of alcohol, relative to nonbingers. Binge status was not associated with impulsivity task performance, while preload type (alcohol/placebo) supported only marginal associations. Conclusions: Risk of binge drinking in nondependent individuals is not strongly affected by impulsive personality characteristics or alcohol's ability to induce behavioral disinhibition. However, alcohol did lead to a priming effect and bingers were more tolerant to the sedative and lightheaded effects of alcohol relative to placebo. Risk of binge drinking is associated with the subjective effects of a priming dose of alcohol.

Rubio M; de Miguel R; Fernandez-Ruiz J; Gutierrez-Lopez D; Carai MAM; Ramos JA. Effects of a short-term exposure to alcohol in rats on FAAH enzyme and CB1 receptor in different brain areas. Drug and Alcohol Dependence 99(1-3): 354-358, 2009. (25 refs.)

Acute alcohol exposure in rats (8% ethanol in the liquid diet for a period of 24 h) is associated with a decrease in the levels of endocannabinoids (anandamide and 2-arachidonoyl-glycerol) as well as in various N-acylethanolamines, in different brain regions. In the present study, we wanted to further explore: (i) whether these decreases might be caused by an increase in fatty acid amide hydrolase (FAAH), the enzyme involved in the degradation of N-acylethanolamines including anandamide, and (ii) whether the changes in endocannabinoid levels are accompanied by parallel changes in the major cannabinoid receptor type, the CB, receptor, activated by these ligands in the brain. Our data proved that FAAH activity did not increase in any of the four regions analyzed, even it was reduced in the hypothalamus and the prefrontal cortex. Paradoxically, FAAH levels increased in the hypothalamus and, to a lesser extent, in the prefrontal cortex and the amygdala, but not in the caudate-putamen. By contrast, the levels of CB, receptors were markedly reduced in the amygdala and prefrontal cortex of these rats, although no changes were seen in the hypothalamus and the caudate-putamen. These results suggest that reductions in the levels of endocannabinoids and related N-acylethanolamines caused by acute alcohol exposure are not originated by an enhanced degradation by FAAH enzyme, but they are associated with low levels of the receptors activated by these ligands, although this parallelism did not Occur in all brain regions analyzed. In any case, these observations would support the notion of a general reduction in the activity of the cannabinoid signaling system by acute alcohol exposure.

Rueger SY; McNamara PJ; King AC. Expanding the utility of the Biphasic Alcohol Effects Scale (BAES) and Initial Psychometric support for the Brief-BAES (B-BAES). Alcoholism: Clinical and Experimental Research 33(5): 916-924, 2009. (43 refs.)

The utility of one of the most widely used subjective alcohol assessment tools, the Biphasic Alcohol Effects Scale (BAES) has been somewhat limited based on lack of psychometric studies in large and diverse samples, a range of alcohol doses, the length of the measure, and the original instructional set which precluded baseline measurement and disclosed to subjects that they received alcohol. The current study investigated the factor structure of the BAES with a modified instructional set at pre-drink baseline and after consumption of various doses of alcohol, in a sample of 190 men and women, heavy and light social drinkers. This study tested the psychometric properties of a brief version of the BAES (Brief-BAES or B-BAES). Results demonstrated robust support of the stimulant and sedative constructs across all conditions, and demonstrated strong psychometric support for the 6-item B-BAES. This is the first comprehensive study to expand the utility of the BAES by instructional set, baseline measurement, at various alcohol doses, and by drinking history and sex. In addition, the introduction of the B-BAES may further increase the utility of this scale, particularly in paradigms with repeated measurement or time constraints.

Sakurai S; Cui R; Tanigawa T; Yamagishi K; Iso H. Alcohol consumption before sleep is associated with severity of sleep-disordered breathing among professional Japanese truck drivers. Alcoholism: Clinical and Experimental Research 31(12): 2053-2058, 2007. (31 refs.)

Background: Alcohol consumption as well as overweight is known to aggravate the severity of sleep-disordered breathing (SDB), but little is known about alcohol consumption in truck drivers. The aim of this study was to examine the relationship between alcohol consumption and SDB among truck drivers. Methods: We conducted a cross-sectional study of 1,465 men aged 20-69 years who were registered with the Japanese Trucking Association. The 3% oxygen desaturation index (3%ODI) was selected as an indicator of SDB, representing the number of desaturation events per hour of recording time in which blood oxygen fell by >= 3% based on overnight pulse-oximetry. Participants completed a self-administered questionnaire including alcohol consumption on the same night for SDB assessment. Results: The prevalence of 3%ODI >= 5, >= 10, and >= 15/h was 25.4%, 11.1%, and 6.6% respectively. The multivariable odds ratios (OR) of 3%ODI >= 10/h were 1.5(0.9-2.5) for 0.5 to < 1.0 g of alcohol intake/kg and 3.4(1.8-6.6) for >= 1.0 g of alcohol intake/kg compared with non-drinkers. Similar associations with alcohol consumption were observed for 3%ODI >= 5 and >= 15/h. The relation between alcohol consumption (>= 1.0 g of alcohol intake/kg) and 3%ODI >= 10/h tended to be more evident among men with body mass index (BMI) < 23.4 kg/m(2) than those with BMI >= 23.4 kg/m(2) [11.4 (3.2-41) vs. 1.2 (0.6-2.7), p = 0.18 for interaction]. A similar trend was observed for 3%ODI >= 5/h. Conclusion: The prevalence of undiagnosed SDB and the significant association of alcohol consumption with SDB severity emphasize the need for SDB screening and alcohol modification as well as weight control to prevent and control SDB among truck drivers.

Schmid B; Hohm E; Blomeyer D; Zimmermann US; Schmidt MH; Esser G et al. Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk. Alcohol and Alcoholism 42(3): 219-225, 2007. (45 refs.)

Aims: To investigate whether concurrent alcohol and tobacco use during early adolescence characterizes a subgroup that differs from users of one substance only regarding several risk factors for later substance use problems. Methods: Participants were from a prospective longitudinal cohort study of 384 children at risk for later psychopathology, with the majority being born with obstetric complications and psychosocial adversities. Assessments of adolescent drug consumption and related intrapersonal characteristics were obtained at age 15. Results: Compared to consumers of alcohol only, 15-year-olds drinking and smoking during the same time period (past 4 weeks) had significantly higher levels of consumption and more excessive use of alcohol, started drinking at an earlier age, had higher scores on the Fagerstrom Test for Nicotine Dependence, and more cannabis use. This group could be distinguished from users of alcohol only by higher novelty seeking and more positive alcohol effect expectancies. Compared to consumers of tobacco only, concurrent users reported higher nicotine dependence and more cannabis use. No significant differences were observed regarding frequency and age at initiation of tobacco use, tobacco-related sensitivity, self-efficacy and instrumentality as well as novelty seeking. Conclusions: Concurrent alcohol and tobacco use during early adolescence is associated with characteristics that are well known as risk factors for later alcohol use problems and dependence and that should be targeted by prevention programs.

Schoenmakers T; Wiers RW; Field M. Effects of a low dose of alcohol on cognitive biases and craving in heavy drinkers. Psychopharmacology 197(1): 169-178, 2008. (46 refs.)

Rationale: Heavy alcohol drinking increases the incentive salience of alcohol-related cues. This leads to increased appetitive motivation to drink alcohol as measured by subjective craving and cognitive biases such as attentional bias and approach bias. Although these measures relate to the same construct, correlations between these variables are often very low. Alcohol consumption might not only increase different aspects of appetitive motivation, but also correlations between those aspects. Objectives To investigate the effect of a low alcohol dose on changes in various measures of appetitive motivation. Materials and methods Twenty-three heavy social drinkers were tested in 2 sessions, once after receiving an alcohol prime dose and once after receiving a placebo drink. After drink administration, attentional bias was measured with a visual-probe task using concurrent eye movement monitoring. Furthermore, we measured the approach bias with a stimulus response compatibility task and subjective craving with the Desires for Alcohol Questionnaire. Results: After the alcohol prime dose, participants had higher levels of craving and more pronounced attentional bias (faster reaction times to probes that replaced alcohol rather than control pictures, increased maintenance of gaze on alcohol pictures, and a higher percentage of first eye movements directed toward alcohol pictures). Approach bias was not influenced by the alcohol prime dose. The correlation between attentional bias and approach bias was significantly higher after the alcohol than after the placebo drink. Conclusions: A low alcohol dose increased most measures of appetitive motivation for alcohol and increased the interrelation between cognitive measures of this construct.

Schuckit MA; Smith TL; Danko GP; Pierson J; Hesselbrock V; Bucholz KK et al. The ability of the self-rating of the effects of alcohol (SRE) scale to predict alcohol-related outcomes five years later. Journal of Studies on Alcohol and Drugs 68(3): 371-378, 2007. (41 refs.)

Objective: A low level of response (LR) to alcohol as measured through alcohol challenges is an early-appearing, genetically influenced characteristic that predicts the risk of heavier drinking and alcohol problems. A less expensive and more easily used measure of LR, the retrospective Self-Rating of the Effects of Alcohol (SRE) questionnaire, also relates to alcohol intake and problems but has not been evaluated for its ability to predict alcohol-related problems 5 years later. Method: At Time 1, 95 18- to 35-year-old (mean age: 25.9 years) subjects who were offspring from families participating at the San Diego site of the Collaborative Study on the Genetics of Alcoholism (COGA) were administered the SRE and evaluated regarding alcohol, drug, and demographic characteristics using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview. Follow-up interviews (Time 2) using the SSAGA were completed an average (SD) of 5.4 (1.34) years later for approximately 80% of the original sample. Results: The retrospective SRE score at Time I (the number of drinks for effects the first five times [First 5] of drinking) correlated with Time 2 maximum quantity and frequency, alcohol problems overall, the number of alcohol-dependence items endorsed, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of alcohol abuse or dependence. The relationships remained robust in hierarchical logistic regression analyses even in the context of age, gender, the number of SRE items endorsed, and alcohol use and problem variables at Time 1. The regressions explained between 21% and 43% of the variance of the outcomes overall, with the First 5 SRE score alone accounting for between 4% and 14%. Conclusions: These findings are consistent with the ability of SRE-based LR scores at Time 1 to predict alcohol-related outcomes over the subsequent 5 years.

Schuckit MA; Smith TL; Danko GP; Trim R; Bucholz KK; Edenberg HJ et al. An evaluation of the full level of response to alcohol model of heavy drinking and problems in COGA offspring. Journal of Studies on Alcohol and Drugs 70(3): 436-445, 2009. (49 refs.)

Objective: The low level of response (LR) to alcohol is an endophenotype related to heavier drinking and alcohol problems. Structural equation models (SEMs) indicate LR affects alcohol outcomes (ALCOUT) both directly and through mediation by drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope with stress (COPE), with some variation depending on the sample tested. This article presents the first full test of this LR-based model in young subjects from the Collaborative Study on the Genetics of Alcoholism (COGA). Method: Data were generated from 325 12- to 22-year-old (47.4% male) drinking offspring from COGA families, using the Self-Report of the Effects of Alcohol questionnaire to determine LR early in the drinking career and a validated, structured interview for demography and alcohol use/problem patterns. Standardized questionnaires were used to measure PEER, EXPECT, and COPE, with the model tested through the maximum likelihood estimation for analyses of the variance/covariance matrix using both Amos and Mplus. Results: The SEM yielded good fit characteristics and explained 59% of the variance, with LR relating both directly to ALCOUT and as partially mediated by PEER and COPE. Although GENDER related to both LR and ALCOUT in the model, and AGE related to ALCOUT, the SEM results were invariant across both AGE and GENDER, with generally similar invariant results regarding the presence or absence of an alcohol-use disorder diagnosis. Conclusions: The results support the applicability of the LR-based model of heavy drinking and alcohol problems in the COGA offspring, a group with different demography compared with the two other samples of adolescents tested to date. The modest differences observed across samples will be evaluated in future research to enhance understanding of how the model operates across socioeconomic groups.

Schuckit MA; Smith TL; Trim R; Heron J; Horwood J; Davis JM et al. The performance of elements of a 'level of response to alcohol'-based model of drinking behaviors in 13-year-olds. Addiction 103(11): 1786-1792, 2008. (49 refs.)

Aim: The goals of this paper are to evaluate whether drinking practices among peers mediates the relationship between a low level of response (LR) to alcohol and a person's heavier drinking and alcohol-related problems in 12-14-year-olds. Design: Correlations and structural equation models (SEM) were used to test a hypothesized model of the relationships among key variables in adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal birth cohort study in Bristol, England. Participants These included 688 boys (40.4%) and girls who were offspring of the pregnant women who had been selected as ALSPAC participants in 1991 and 1992. The offspring were interviewed at about age 13 years, and those who had ever consumed a full drink completed the Self-Report of the Effects of Alcohol (SRE) questionnaire indicating the number of drinks required for up to four effects early in their drinking histories. A higher number of drinks required for effects indicated a low LR per drink consumed. Findings: The SEM explained 58% of the variance of the alcohol pattern, and had good fit characteristics. A low LR was related to heavier drinking and more alcohol problems both directly and as mediated partially by drinking in peers. The model performed well across the narrow age range, and applied equally well in boys and girls. Conclusions The perceived drinking practices of peers is a potentially important mediator of how a low LR to alcohol relates to drinking practices during early adolescence. The findings may be useful in developing approaches to prevent heavier drinking in this young group.

Schuckit MA; Smith TL; Trim R; Kreikebaum S; Hinga B; Allen R. Testing the level of response to alcohol-based model of heavy drinking and alcohol problems in offspring from the San Diego Prospective Study. Journal of Studies on Alcohol and Drugs 69(4): 571-579, 2008. (64 refs.)

Objective: The low level of response (LR) to alcohol, an endophenotype related to heavy drinking and alcohol problems, influences the risk for alcoholism in the context of additional life domains. This article evaluates an LR-based model of drinking patterns in 113 drinking offspring, ages 12 to 24 years, from the San Diego Prospective Study. Method: Correlations and structural equation models (SEMs) were evaluated using LR as measured from the Self-Report of the Effects of Alcohol questionnaire in the offspring. The expectations of the effects of alcohol (EXPECT), the perception of drinking in peers (PEER), the use of alcohol to cope with stress (COPE), and the drinking quantities and alcohol-related problems (ALCOUT) were evaluated in the SEM. Results: The LR-based model worked well, with good fit characteristics and 78% of the variance of outcome explained. LR related directly to ALCOUT, with additional mediation of that relationship through EXPECT and COPE. Conclusions: The LR-based model performed well in adolescents from the San Diego Prospective Study. Knowledge of which domains mediate how LR impacts alcohol-related outcomes may be useful in developing more focused and potentially more effective prevention approaches.

Schuckit MA; Smith TL; Trim RS; Heron J; Horwood J; Davis J et al. The self-rating of the Effects of Alcohol Questionnaire as a predictor of alcohol-related outcomes in 12-year-old subjects. Alcohol and Alcoholism 43(6): 641-646, 2008. (40 refs.)

Aims: A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. To date, only one study has evaluated the predictive validity of a second measure of LR as determined by the Self-Report of the Effects of Alcohol (SRE) Questionnaire. The current analyses evaluate the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom. Methods: The subjects were 156 boys (54.5%) and girls from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. Results: The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. Conclusion: The SRE scores appear to have value in predicting future heavier drinking and alcohol problems in 12-year olds that go beyond the information offered by the earlier drinking pattern alone.

Sisson JH. Alcohol and airways function in health and disease. (review). Alcohol 41(5): 293-307, 2007. (101 refs.)

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Sumnall HR; Beynon CM; Conchie SM; Riley SCE; Cole JC. An investigation of the subjective experiences of sex after alcohol or drug intoxication. Journal of Psychopharmacology 21(5): 525-537, 2007. (85 refs.)

Despite long-standing concern over the sexual health of the population there has been little work undertaken in the UK investigating sexual risk taking and sexual behaviours in the context of substance use. To investigate this further, 270 non-drug treatment seeking members of the public aged between 18 and 66 were administered a questionnaire containing the Alcohol Use Disorders Identification Test (AUDIT), the Drug Abuse Screening Test (DAST), the Severity of Dependence Scale (SDS), the Sexual Risks Scale and Attitudes toward condom use (SRSA), the Sexual Sensation Seeking Scale (SSSS); the Hospital Anxiety and Depression Scale (HADS), and questions pertaining to sexual episodes proximal to substance use. The population reported a varied history of substances and despite there not being self-awareness of problematic drug use, 39.4% reported above the cut-off mark of six on the DAST. An even greater percentage (57.8%) reported a score above eight on the AUDIT indicating hazardous or harmful drinking behaviour. The substance most often associated with sexual episodes was alcohol, followed by cannabis and ecstasy, and all were most frequently consumed in private houses. Sexual activity after drug use was most frequently circumstantial (i.e. the individual hadn't taken the substance for the specific purposes of sex), and was significantly associated with use of cannabis and ecstasy. The second most frequently reported association between drug use and sex was facilitation of a sexual encounter (i.e. to lower sexual inhibitions, increase self esteem and confidence), which was associated with use of alcohol, cannabis, cocaine and ecstasy. Although it was not possible to identify differences in subjective sexual changes after use of particular drugs, subjects reported that compared to sex after alcohol, sex on other drugs was more pleasurable and satisfying, with a greater perception of interpersonal contact with the partner and a greater willingness to sexually experiment. However, this latter change was not associated with changes in the type of sexual activity engaged in. Regression analysis revealed that the greatest subjective changes in sexual experiences were reported by younger participants who had ingested either ecstasy or cannabis prior to the sexual episode. These results are discussed in the context of sexual risk taking and suggest areas of intervention focus which may address substance use and sexual risk taking together.

Szabo G. Moderate drinking, inflammation, and liver disease. Annals of Epidemiology 17(5, Supplement S): S49-S54, 2007. (28 refs.)

It is well known that heavy drinking increases the risk of alcohol-related liver disease (ALD). Female gender, hepatitis C or B, obesity, and other cofactors increase susceptibility to ALD, so "safe" levels of alcohol consumption in regard to ALD vary among individuals. Inflammation is one mechanism by which alcohol causes liver damage. Increasing evidence suggests that in contrast to the proinflammatory activation by chronic excessive alcohol consumption, acute moderate alcohol administration has anti, inflammatory effects. Long-term alcohol administration results in increased baseline nuclear regulatory factor kappa B (NF-kappa B) activation in the livers of mice; in contrast, acute alcohol administration in mice attenuates lipopolysaccharide (LPS)-induced NF-kappa B activation in the liver and serum tumor necrosis factor alpha (TNF alpha) induction. Consistent with this notion, peripheral blood monocytes from patients with alcoholic hepatitis spontaneously produce increased amounts of TNF alpha and respond to ex vivo LPS stimulation with increased TNF alpha levels, while acute moderate alcohol consumption in normal volunteers results in the attenuation of TNF alpha production by various stimulants and attenuates monocyte production of other proinflammatory cytokines. To date, no evidence for a beneficial role of the anti-inflammatory effect of acute moderate alcohol consumption on the liver has been demonstrated, but this may contribute to the effect of alcohol on other organ systems.

Szabo G; Mandrekar P; Oak S; Mayerle J. Effect of ethanol on inflammatory responses: Implications for pancreatitis. (review). Pancreatology 7(2/3): 115-123, 2007. (45 refs.)

Background/Aims: Alcohol use alters inflammatory cell responses. While alcohol has direct effects on pancreatic acinar cells, activation of inflammatory cells is a major component of the pathology of alcoholic pancreatitis. Methods: The effects of acute or chronic alcohol exposure were evaluated in human monocytes on the production of TNF alpha or IL10 production, pro-inflammatory gene and nuclear factor-kappa B (NF-kappa B) activation. Results: Moderate, acute alcohol consumption or equivalent doses of alcohol in vitro had anti-inflammatory effects on monocyte activation via inhibition of pro-inflammatory genes and NF-kappa B activation, inhibition of TNF alpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol treatment augmented NF-kappa B activation and TNF alpha production and inhibited IL-10 levels in the presence of complex stimulation with combined TLR2 and TLR4 ligands. Prolonged alcohol exposure also resulted in an increase in NF-kappa B and TNF alpha production in response to TLR4 stimulation with LPS. Conclusion: These results suggest that alcohol can either attenuate or promote inflammatory responses that are critical in pancreatitis. Our results support the hypothesis that both acute alcohol intake in the presence of complex stimuli (such as necrotic cells) and chronic alcohol exposure result in hyper-responsiveness of monocytes to inflammatory signals and may contribute to increased inflammation in pancreatitis.

Tambour S; Brown LL; Crabbe JC. Gender and age at drinking onset affect voluntary alcohol consumption but neither the alcohol deprivation effect nor the response to stress in mice. Alcoholism: Clinical and Experimental Research 32(12): 2100-2106, 2008. (27 refs.)

Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless, relatively few studies using animal models have investigated the relationship between age of onset of drinking and ethanol drinking patterns in adulthood. Besides age at drinking onset, other factors such as gender could also affect the pattern of development of alcohol consumption. In rodents, many studies have shown that females drink more than males. However, even if it is assumed that hormonal changes occurring at puberty could explain these differences, only one study performed in rats has investigated the emergence of sex-specific alcohol drinking patterns in adolescence and the transition from adolescence to adulthood. The aim of the present study was to compare the acquisition of voluntary alcohol consumption, relapse-like drinking (the Alcohol Deprivation Effect-ADE) and stress-induced alcohol drinking in male and female outbred mice that acquired alcohol consumption during adolescence or adulthood. Separate groups of naive female and male WSC-1 mice aged +/- 28 days (adolescents) or +/- 70 days (adults) were given ad libitum access to water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2-week deprivation phase (9th and 10th week). After the deprivation period, 2-bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th). During the 13th week, all animals were subjected to restraint stress for 2 consecutive days. Over the entire time course of the experiment, ethanol intake and preference increased in females (both adults and adolescents). Adolescent animals (both females and males) showed a transient increase in alcohol consumption and preference compared to adults. However, by the end of continuous alcohol exposure (when all mice were adults), ethanol intake was not affected by age at drinking onset. A deprivation phase was followed by a rise in ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not alter alcohol self-administration either during or after its occurrence. Emergence of greater alcohol consumption in adult females does not seem to be limited to a specific developmental period (i.e., puberty). Age of voluntary drinking onset (adolescence vs. adulthood) does not affect eventual alcohol intake in adult WSC-1 mice and does not modify the transient increase in ethanol consumption after alcohol deprivation.

Taylor RE; Raysor BR; Kwagyan J; Ramchandani VA; Kalu N; Powell-Davis M et al. Alterations in ethyl alcohol pharmacokinetics during oral consumption of malt liquor beverages in African Americans. Alcoholism: Clinical and Experimental Research 32(12): 2074-2080, 2008. (36 refs.)

Malt liquor (ML) beverages have become increasingly popular among urban minority groups, due partly to their inexpensive price and targeted advertising. We hypothesized that nonfermented by-products contained in ML beverages will alter the pharmacokinetics (PK) and pharmacodynamic (PD) effects of its ethanol content. In addition, we determined the effect of alcohol dehydrogenase (ADH) genotypes on the PK following consumption of ML beverages. The study was conducted in 31 healthy adult African-American social drinkers, mean +/- SD age of 22.3 +/- 1.3 years, and weight of 70.7 +/- 10.9 kg. Participants were administered ethanol, in randomized order, 2-weeks apart, in the form of oral ML beverage (6%v/v), or isocaloric solution of diet soda-ethanol (DS-Etoh) beverage (6%v/v). During each session the beverage was consumed over 4 minutes and breath alcohol concentrations (BrAC) as well as subjective and behavioral effects of ethanol were evaluated over 180 minutes. Pharmacokinetic parameters of ethanol were calculated using Michaelis-Menten elimination kinetics. The effect of ML and ADH genotype on PK was evaluated using the Wilcoxon rank-sum test and the Wilcoxon signed rank test, respectively. Results show a slower mean rate of absorption, K-a, (0.12 vs. 0.15 min(-1), p = 0.03) and a longer time to reach maximum concentration, T-max, (28 vs. 23 minute, p < 0.01) for the ML compared with DS-Etoh beverage. The ML beverage resulted in a larger area under the BrAC-time curve compared with DS-Etoh beverage (8.4 vs. 6.8 min g/dl, p = 0.02). There was no difference in the subjective PD effects between the 2 beverages. Results show that exposure to ethanol following the consumption of ML beverages is different compared to that following nonmalt beverages in African-Americans. These differences may be related to nonfermented by-products present in commercially available ML products. These PK differences do not appear to result in significant perceived alcohol PD changes, nor are they related to ADH genotype.

Terry P; Doumas M; Desai R; Wing A. Dissociations between motor timing, motor coordination, and time perception after the administration of alcohol or caffeine. Psychopharmacology 202(4): 719-729, 2009. (66 refs.)

The impacts of psychoactive drugs on timing have usefully informed theories of timing and its substrates. The objectives of the study are to test the effects of alcohol and caffeine on the explicit timing involved in tapping with the implicit timing observed in the coordinated picking up of an object, and with the temporal discrimination. Participants in the "alcohol" experiment (N = 16) received placebo, "low" (0.12 g/kg or 0.14 g/kg for women/men, respectively) or "high" (0.37 g/kg or 0.42 g/kg, respectively) doses of alcohol, and those in the "caffeine" experiment (N = 16) received placebo, 200 or 400 mg caffeine. Time production variability was measured by repetitive tapping of specified intervals, and sources of variance attributable to central timer processes and peripheral motor implementation were dissociated. The explicit timing in tapping was compared with the implicit timing in the coordinated picking up of an object. Time perception was measured as discrimination thresholds for intervals of similar duration. Drug effects on reaction time were also measured. For tapping, alcohol significantly increased timer variability, but not motor variability; it did not affect coordination timing in the grip-lift task. Conversely, for time perception, the low dose of alcohol improved temporal discrimination. Caffeine produced no effects on any of the timing tasks, despite significantly reducing reaction times. The effects of alcohol argue against a common clock process underlying time interval perception and production in the range below 1 s. In contrast to reaction time measures, time perception and time production appear relatively insensitive to caffeine.

Tizabi Y; Bai L; Copeland RL; Taylor RE. Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell. Alcohol and Alcoholism 42(5): 413-416, 2007. (38 refs.)

Aims: This study was undertaken to determine whether simultaneous administration of both alcohol and nicotine systemically would result in an additive dopamine release in the nucleus accumbens (NACC). Moreover, to also investigate whether nicotinic receptors may be mediating these effects of alcohol and nicotine, the effects of mecamylamine, a nicotinic receptor antagonist was also evaluated. Methods: Microdialysis was applied to measure the dopamine overflow in the shell region of NACC. All drugs were administered intraperitoneally. The doses of alcohol ranged from 0.52.0 g/kg, and nicotine and mecamylamine 0.251.0 mg/kg. Results: An additive effect of combined alcohol and nicotine on dopamine release was obtained. This effect of alcohol and nicotine was dose-dependently blocked by mecamylamine pre-treatment. Conclusions: These findings further support the hypothesis that an additive effect of alcohol and nicotine on the mesolimbic reward pathway may contribute to the high incidence of smoking in alcoholics. Furthermore, nicotinic antagonists can block such effects of combined alcohol and nicotine.

Tousoulis D; Ntarladimas I; Antoniades C; Vasiliadou C; Tentolouris C; Papageorgiou N et al. Acute effects of different alcoholic beverages on vascular endothelium, inflammatory markers and thrombosis fibrinolysis system. Clinical Nutrition 27(4): 594-600, 2008. (34 refs.)

Background & aim: Mild alcohol consumption has been associated with decreased cardiovascular risk, although the underlying mechanisms are still unclear. We compared the acute effects of several alcoholic beverages on endothelial. function, inflammatory process and thrombosis/fibrinolysis system in young adults. Methods: In this randomized intervention trial, healthy young individuals with no risk factor for atherosclerosis were randomized into 5 equally sized groups and received an equal amount of alcohol (30 g), as red wine (264 ml), white wine (264 ml), beer (633 ml.), whisky (79 ml.) or water (250 ml.). Forearm blood flow was determined by gauge-strain plethysmography, at baseline, 1 and 4 In after alcohol. intake. Levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen (Fib), plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF) and tissue plasminogen activator (tPA) were determined at baseline and 4 h after alcohol consumption. Results: Reactive hyperemia was significantly increased 1 h after beer and red wine consumption (p < 0.05 for both), while it returned at baseline at 4 h (p = ns vs baseline) but remained unchanged in all. the other groups. vWF was decreased in the beer and red wine groups (p < 0.05 for both) only. PAI-1/tPA ratio remained unchanged only in red wine and control. group. Inflammatory markers remained unchanged in all the groups. Conclusions: Acute consumption of red wine or beer improves endothelial function and decreases vWF levels, suggesting that the type of beverage may differently affect endothelial function and thrombosis/fibrinolysis system in healthy adults.

Trevisan L; Petrakis IL; Pittman B; Gueorguieva R; D'Souza DC; Perry E et al. Absence of significant interactive effects of high-dose D-cycloserine and ethanol in healthy human subjects: Preliminary insights into ethanol actions at the Glycine(B) site of NMDA glutamate receptors. Alcoholism: Clinical and Experimental Research 32(1): 36-42, 2008. (61 refs.)

Background: Ethanol reduces N-methyl-D-aspartate (NMDA) glutamate receptor function via multiple cellular targets. It is not yet clear whether direct ethanol antagonism of the glycine(B) co-agonist site of NMDA receptors is relevant to this effect. The purpose of this study was to evaluate whether ethanol effects at the glycine(B) co-agonist site was clinically relevant by evaluating some aspects of the psychopharmacologic interactions between the glycine(B) partial agonist, D-cycloserine (DCS), and ethanol in healthy human subjects. Methods: All subjects completed 4 test days under double-blind conditions in which DCS or placebo was administered orally prior to ethanol or an ethanol-tainted placebo drink. Two groups of healthy subjects were studied. A first group of subjects (n = 25) were pretreated orally with DCS 500 mg or placebo 4 hours prior to ethanol (0.8 g/kg, p.o. or placebo) administration. A second group of subjects (n = 20) were pretreated with DCS 1000 mg or placebo prior to ethanol administration. Outcomes included subjective and cognitive responses to the experimental interventions. Results: Predictable ethanol responses were observed in both groups of subjects, although the response to ethanol and the breath alcohol levels, but not plasma alcohol levels, were slightly but significantly lower in the group that received the higher DCS dose. DCS produced mild sedative effects that were greater for the lower than the higher dose. It also produced a mild impairment of verbal fluency without impairing attention. No statistically significant interactions between ethanol and DCS emerged in analyses. However, the combination of ethanol and DCS produced significantly greater impairment than both ethanol or DCS administered alone on a test of verbal fluency and aspects of memory function. Implications: DCS and ethanol both produced sedative and cognitive effects, consistent with their ability to reduce NMDA receptor function. However, the absence of interactive effects observed in this study raises questions about the clinical significance of the glycine(B) site as a target for ethanol in the brain at levels of ethanol intoxication associated with social drinking. However, it should be noted that this conclusion is limited to the dependent measures evaluated and the doses of ethanol and DCS studied.

Trim RS; Schuckit MA; Smith TL. Level of response to alcohol within the context of alcohol-related domains: An examination of longitudinal approaches assessing changes over time. Alcoholism: Clinical and Experimental Research 32(3): 472-480, 2008. (53 refs.)

Background: The manner in which a low level of response (LR) to alcohol relates to domains that enhance the risk for heavy drinking has traditionally been studied through cross-sectional models. However, many of the relevant domains, such as the maximum number of drinks consumed in 24 hours (MAXDRINK) and drinking among peers (PEER) typically decrease across adulthood. This study evaluated whether a person's LR to alcohol predicted alcohol-related domains at multiple time-points and examined longitudinal relations among these domains in a sample of probands from the San Diego Prospective Study. Methods: LR to alcohol was assessed in 174 male probands from the San Diego Prospective Study at baseline (T1), and measures of MAXDRINK, PEER, and drinking to cope (COPE) were collected at the 15-year (T15), T20, and T25 follow-ups. Results: A low LR to alcohol at T1 predicted higher levels of MAXDRINK and COPE at T15, consistent with prior studies. Using latent growth curve models, higher levels of T15 MAXDRINK predicted less decreases in PEER drinking over time. Additional analyses found a time-specific effect of T20 COPE on T25 MAXDRINK even after accounting for the growth factors of both domains. Conclusion: These evaluations illustrate that LR prospectively predicted relevant outcomes, and clarify how alcohol-related domains related to each other as the probands progressed through middle adulthood. Treatment implications are discussed and drinking to cope may be an important intervention target for problematic alcohol use.

Waszkiewicz N; Szajda SD; Jankowska A; Kepka A; Dobryniewski J; Szulc A et al. The effect of the binge drinking session on the activity of salivary, serum and urinary beta-hexosaminidase: Preliminary data. Alcohol and Alcoholism 43(4): 446-450, 2008. (32 refs.)

Our report is the first to show that an acute ingestion (6 h) of a relatively large, yet tolerable dose of alcohol (120-160 g), significantly increases activity of total serum beta-hexosaminidase (total beta-HEX), beta-HEX A and beta-HEX B isoenzymes, as well as salivary total beta-HEX and urinary beta-HEX A, in eight infrequent binge drinkers. An increase in the activity of serum and urinary total HEX is mainly due to its secretory isoenzyme beta-HEX A.

Waszkiewicz N; Szajda SD; Jankowska A; Zwierz P; Czernikiewicz A; Szulc A et al. The effect of acute ethanol intoxication on salivary proteins of innate and adaptive immunity. Alcoholism: Clinical and Experimental Research 32(4): 652-656, 2008. (48 refs.)

Background: Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. Methods: Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6-hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. Results: At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). Conclusion: Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.

Weiss E; Marksteiner J. Alcohol-related cognitive disorders with a focus on neuropsychology. (review). International Journal on Disability and Human Development 6(4): 337-342, 2007. (55 refs.)

The aim of this paper is to discuss how acute and chronic alcohol consumption affects on cognitive functions. In general, greater deficits in executive functions compared with other cognitive functions have been reported in patients suffering from alcohol addiction with deficits in problem solving, abstraction, planning, organizing and working memory. The acute effects of alcohol cause a decline in explicit memory processes. Alcohol impairs memory formation, at least in part, by disrupting activity in the hippocampus. Persisting neuropsychological deficits after cessation of alcohol consumption may lead to alcohol amnestic disorder and dementia associated with alcoholism. Considerable inconsistencies in neuropsychological study results will be discussed referring to variations in methodological designs such as amount of alcohol assumed or length of alcohol abuse. Despite advances in human neuroimaging techniques, detecting clear relations between brain structures and specific cognitive functions has so far been difficult.

Weitlauf C; Woodward JJ. Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex. Alcoholism: Clinical and Experimental Research 32(4): 690-698, 2008. (52 refs.)

Background: Brain imaging studies have revealed abnormal function in the prefrontal cortex (PFC) of alcoholics that may contribute to the impulsive behavior and lack of control over drinking that characterizes this disorder. Understanding how ethanol affects the physiology of PFC neurons may help explain this loss of control and lead to better treatments for alcohol addiction. In a previous study from this laboratory, we showed that ethanol inhibits complex patterns of persistent activity (known as "up-states") in medial PFC (mPFC) neurons in a reversible and concentration-dependent manner. Methods: In the current study, whole-cell patch clamp recordings were used to directly examine the effects of ethanol on the glutamatergic and GABAergic components that underlie persistent activity. Results: In deep-layer mPFC pyramidal neurons, ethanol reversibly attenuated electrically evoked N-methyl-D-aspartate-type glutamate receptor (NMDAR)-mediated EPSCs. Significant inhibition was observed at concentrations as low as 22 mM, equivalent to a blood ethanol concentration (0.1%) typically associated with legal limits for intoxication. In contrast to NMDA responses, neither evoked nor spontaneous EPSCs mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptor were affected by ethanol at concentrations as high as 88 mM, a concentration that can be fatal to non-tolerant individuals. At similar concentrations, ethanol also had little effect on spontaneous or evoked IPSCs mediated by a-type gamma-aminobutyric acid receptor. Finally, mPFC neurons showed little evidence of GABAR-mediated tonic current and this was unaffected by ethanol. Conclusions: Together, these results suggest that NMDAR-mediated processes in the mPFC may be particularly susceptible to disruption following the acute ingestion of ethanol.

Wolf A; Bray GA; Popkin BM. A short history of beverages and how our body treats them. Obesity Reviews 9(2): 151-164, 2008. (77 refs.)

Numerous studies have demonstrated that beverages containing sugar, high fructose corn syrup (HFCS) or alcohol are handled differently by the body than when sugar or HFCS are incorporated in solid foods and as a result the overall caloric intake from solid food does not adjust to account for the calories in these beverages. A consideration of our evolutionary history may help to explain our poor compensatory response to calories from fluids. This paper reviews the history of eight important beverages: milk, beer, wine, tea, coffee, distilled alcoholic beverages, juice and soft drinks. We arrive at two hypotheses. First, humans may lack a physiological basis for processing carbohydrate or alcoholic calories in beverage because only breast milk and water were available for the vast majority of our evolutionary history. Alternatives to those two beverages appeared in the human diet no more than 11 000 years ago, but Homo sapiens evolved between 100,000 and 200,000 years ago. Second, carbohydrate and alcohol-containing beverages may produce an incomplete satiation sequence which prevents us from becoming satiated on these beverages.

Woodward JJ. GABA(A) alpha 4 receptor subunits and ethanol: A knockout punch? (editorial). Alcoholism: Clinical and Experimental Research 32(1): 8-9, 2008. (3 refs.)

This editorial provides a reflection on two papers in this issue. The author notes that "Defining the molecular sites of action that account for the neurobehavioral effects of ethanol has been an especially difficult task. Both membrane lipids and the proteins that reside there have been examined as targets for the modest and unassuming ethyl alcohol molecule. Over the last 20 years, a great deal of this attention has focused on the widely expressed GABAA family of chloride-conducting ion channels that mediate much of the inhibitory neurotransmission in the adult brain. This is due in large part to the similarities observed between the behavioral actions of ethanol and compounds such as benzodiazepines and barbiturates that are known modulators of GABAA receptor function." Two papers in this issue examine the effects of ethanol in animals that lack the a4 gene. If a4 containing receptors are an important target for the actions for ethanol, then animals lacking this site should display profound alterations in their response to ethanol. However, this was true but with limits, findings that were unexpected. The possible explanations for this and the insights these findings shed is noted, namely the complexities of the pheonomenon being studies.

Yoda T; Crawshaw LI; Saito K; Nakamura M; Nagashima K; Kanosue K. Effects of alcohol on autonomic responses and thermal sensation during cold exposure in humans. Alcohol 42(3): 207-212, 2008. (24 refs.)

We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during cold exposure in humans. Eight healthy men (mean age 22.3 +/- 0.7 year) participated in this study. Experiments were conducted twice for each subject at a room temperature of 18 degrees C. After a 30-min resting period, the subject drank either 15% alcohol at a dose of 0.36 g/kg body weight (alcohol session) or an equal volume of distilled water (control session), and remained in a sitting position for another 60 min. Mean skin temperature continued to decrease and was similar in control and alcohol sessions. Metabolic rate was lower in the alcohol session, but the difference did not affect core temperature, which decreased in a similar manner in both alcohol and control sessions (from 36.9 +/- 0.1 degrees C to 36.6 +/- 0.1 degrees C. Whole body sensations of cold and thermal discomfort became successively stronger in the control session, whereas these sensations were both greatly diminished after drinking alcohol. In a previous study we performed in the heat, using a similar protocol, alcohol produced a definite, coordinated effect on all autonomic and sentient heat loss effectors. In the current study in the cold, as compared to responses in the heat, alcohol intake was followed by lesser alterations in autonomic effector responses, but increased changes in sensations of temperature and thermal discomfort. Overall, our results indicate that although alcohol influences thermoregulation in the cold as well as in the heat, detailed aspects of the influence are quite different.

Young R; Sweeting H; West P. A longitudinal study of alcohol use and antisocial behaviour in young people. Alcohol and Alcoholism 43(2): 204-214, 2008. (58 refs.)

Aims: To examine the direction of causation between young peoples antisocial behaviour and alcohol (mis)use in the longer and shorter term, together with their joint effects on alcohol-related trouble. Methods: A longitudinal study (2586 pupils) supplied data, allowing exploration of the causal effects of alcohol (mis)use and antisocial behaviour between ages 11 and 15, using structural equation models of longer and shorter-term relationships and joint-effects models in respect of alcohol-related trouble at age 15. This method allowed us to evaluate which of three hypotheses, described as disinhibition [alcohol (mis)use causes or facilitates antisocial behaviour], susceptibility [antisocial behaviour causes alcohol (mis)use] or reciprocal [alcohol (mis)use causes antisocial behaviour and the reverse] receives most support, both overall and by gender, social class, and drinking context. Results: Overall, the results support the susceptibility hypothesis, particularly in the longer-term models. There is no support for pure disinhibition. However, in the shorter-term and joint-effects models (i.e. as the time lag becomes shorter), there is evidence that in some gender, social class, or drinking contexts, in addition to antisocial behaviour causing alcohol (mis)use, the reverse also applies. Conclusions: Antisocial behaviour is the main predictor of alcohol (mis)use and alcohol-related trouble, with alcohol (mis)use impacting only modestly on antisocial behaviour and alcohol-related trouble in the shorter term.

Zacny JP; Walker DJ; Derus LM. Choice of nitrous oxide and its subjective effects in light and moderate drinkers. Drug and Alcohol Dependence 98(1/2): 163-168, 2008. (23 refs.)

Background: Alcohol-drinking status has been shown to modulate the reinforcing and subjective effects of a number of drugs. We have previously published two studies on the modulating effects of alcohol-drinking status on choice for, and subjective effects of, nitrous oxide, but the results were equivocal. Using a methodology different from our previous studies, we sought to determine in a more definitive fashion the degree to which the choice of nitrous oxide and its subjective effects were modulated by drinking status. Methods: Four concentrations of nitrous oxide (0, 20, 30, and 40%) were administered to 16 moderate drinkers (MDs) and 16 light drinkers (LDs) across four 3.5-h sessions. During experimental sessions, subjects first completed two 10-min sampling trials in which one of the nitrous oxide concentrations and placebo (100% oxygen) were inhaled. Subjective and psychomotor tests were given 5 min into each sampling trial. During the subsequent choice period, subjects were allowed to choose what they wanted to inhale (drug, placebo, or "drug-free air") on nine contiguous 5-min choice trials. Results: Choice of nitrous oxide was modulated by drinking status: MDs but not LDs chose nitrous oxide significantly more times than placebo, and MDs also chose nitrous oxide significantly more times than did LDs. At each active nitrous oxide concentration, MDs reported more abuse liability-related subjective effects, especially at the 20% and 30% concentrations. Conclusions: The results of the present study provide more conclusive evidence that choice as well as subjective effects of nitrous oxide is modulated by alcohol-drinking status.

Zhou KY; Zhang L; Xi JK; Tian W; Xu ZL. Ethanol prevents oxidant-induced mitochondrial permeability transition pore opening in cardiac cells. Alcohol and Alcoholism 44(1): 20-24, 2009. (37 refs.)

Aims: The purpose of this study was to determine if ethanol prevents the mitochondrial permeability transition pore (mPTP) opening via glycogen synthase kinase 3 beta (GSK-3 beta). Methods: Cardiac H9c2 cells were exposed to ethanol (10-1000 mu M) for 20 min. GSK-3 beta activity was determined by measuring its phosphorylation at Ser(9). Mitochondrial membrane potential (Delta Psi(m)) was assessed by imaging (confocal microscopy) H9c2 cells loaded with tetramethylrhodamine ethyl ester (TMRE). To activate GSK-3 beta, cells were transfected with constitutively active GSK-3 beta (GSK-3 beta-S9A-HA) mutant plasmid. Results: Treatment of cardiac cells with low doses of ethanol (10-500 mu M) significantly enhanced GSK-3 beta phosphorylation, indicating that ethanol can inactivate GSK-3 beta in H9c2 cells. The effect of ethanol on GSK-3 beta activity was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and ethanol could enhance Akt phosphorylation, implying that the PI3K/Akt pathway accounts for the action of ethanol. Ethanol prevented oxidant (H2O2)-induced loss Delta Psi(m), an effect that was reversed by LY294002, indicating that ethanol can modulate the mPTP opening caused by oxidant stress through the PI3K/Akt pathway. Ethanol failed to preserve Delta Psi(m) in cells transfected with the constitutively active GSK-3 beta (GSK-3 beta-S9A-HA) mutant, suggesting that ethanol prevents the mPTP opening by inactivating GSK-3 beta. Conclusions: These data suggest that ethanol prevents the mPTP opening through inactivation of GSK-3 beta. The PI3K/Akt signaling pathway is responsible for inactivation of GSK-3 beta by ethanol.

Zimmermann US; Buchmann A; Steffin B; Dieterle C; Uhr M. Alcohol administration acutely inhibits ghrelin secretion in an experiment involving psychosocial stress. Addiction Biology 12(1): 17-21, 2007. (23 refs.)

The appetite-regulating hormones leptin and ghrelin are altered in alcoholism and influence the hypothalamic-pituitary-adrenal system. We investigated whether acute ethanol ingestion and stress exposure affect ghrelin secretion. Nine healthy male volunteers were exposed to a standardized laboratory stressor involving public speaking on 2 days. On the first day they ingested 0.6 g/kg ethanol and on the second a placebo drink 50 minutes before the stressor. Plasma ghrelin, cortisol, glucose, and insulin were measured at baseline and in eight subsequent samples obtained up to 120 minutes after drinking (75 minutes after stress onset). The stress test induced a transient and significant rise in cortisol, which was not altered by prior alcohol administration. No significant change of ghrelin, insulin or glucose levels was observed after the stressor. Ghrelin declined significantly within 15 minutes after alcohol drinking, fell to a minimum of 66% of baseline at 75 minutes and remained at that level until the last sample at 120 minutes. No significant ghrelin changes were observed during placebo experiments. Insulin and glucose were not significantly influenced by stress or by alcohol. We conclude that alcohol drinking acutely attenuates circulating ghrelin levels. This effect is more pronounced than would be expected from the calories ingested with alcohol, as compared with a prior report where liquid meals of different caloric content were administered. We could not observe a stress effect on ghrelin, which does not support a role for ghrelin in stress-induced anorexia.

Zisserson RN; Palfai TP. Behavioral Activation System (BAS) sensitivity and reactivity to alcohol cues among hazardous drinkers. Addictive Behaviors 32(10): 2178-2186, 2007. (32 refs.)

Previous research has suggested that Behavioral Activation System (BAS) sensitivity may be associated with stronger appetitive responses to alcohol cues. This study was conducted to explore whether those with higher BAS sensitivity showed greater urge and affective responses to alcohol cues and whether different types of appetitive cues moderated the magnitude of these associations. One hundred eighty-eight hazardous drinkers (90 women) were exposed to the sight and smell of their favorite alcoholic beverage during a cue exposure procedure. Participants were asked to either lean towards the beverage (Cue Only) when signaled by tones, or lift the beverage towards them (Cue+Action). BAS sensitivity was significantly associated with baseline ratings of urge and affect, and was found to be a significant predictor of urge and affect reactivity; however significant interaction effects with cue type were not observed. Results provide further evidence for the influence of individual differences in reward responsiveness on alcohol use and abuse.