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CORK Bibliography: Alcohol. Acute Effects

99 citations. December 2006 to present

Prepared: June 2008

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.

Armeli S; Feinn R; Tennen H; Kranzler HR. The effects of naltrexone on alcohol consumption and affect reactivity to daily interpersonal events among heavy drinkers. Experimental and Clinical Psychopharmacology 14(2): 199-208, 2006. (38 refs.)

The authors examined whether the associations among daily positive and negative interpersonal events, alcohol consumption, and affect varied as a function of naltrexone or placebo administered in a targeted (in anticipation of or in response to high-risk drinking situations) or daily fashion. Heavy drinkers (N = 149) received 4 sessions of brief coping skills counseling in addition to 8 weeks of naltrexone treatment. They recorded for 8 weeks in structured nightly diaries their interpersonal interactions, affect, and alcohol consumption. The authors predicted that participants receiving naltrexone, compared with those taking placebo, would drink less in response to interpersonal encounters and that naltrexone administration would attenuate the link between positive interpersonal events and positive affective states. Results indicated that both positive and negative interpersonal interactions were associated with an increased probability of engaging in any drinking and that positive daily social celebratory events were associated with an increased probability of engaging in heavy drinking. Participants taking naltrexone in a targeted fashion showed the strongest positive association between the number of positives social celebratory events and drinking. Although this finding was inconsistent with the overall reduction in drinking that has been generally reported for those treated with naltrexone, positive social celebratory events occurred on only a minority of days. Participants taking naltrexone, compared with those taking placebo, showed weaker associations between positive social celebratory events and positive and negative affective states. Findings are discussed in terms of naltrexone's dampening effects on the rewarding properties of alcohol use and certain positively valenced stimuli.

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.

Bloor RN; Spanel P; Smith D. Quantification of breath carbon disulphide and acetone following a single dose of disulfiram (Antabuse) using selected ion flow tube mass spectrometry (SIFT-MS). Addiction Biology 11(2): 163-169, 2006. (27 refs.)

Selected ion flow tube mass spectrometry (SIFT-MS) has been used to measure simultaneously the concentrations of both carbon disulphide and acetone in exhaled breath following the ingestion of a single dose of disulfiram (Antabuse). Carbon disulphide is a product of the metabolism of disulfiram and is excreted mainly through the lungs. Acetone is a product of normal metabolism and appears in the breath of all individuals. These breath analyses were performed in single exhalations and the results were available in real time. The levels of breath acetone and carbon disulphide were compared with levels obtained from a control subject who had not ingested disulfiram. Breath carbon disulphide was seen to increase from 15 p.p.b. to 618 p.p.b. over a 28-hour period, in the single individual tested, following ingestion of disulfiram, while acetone levels increased from 300 p.p.b. (normal) to over 4000 p.p.b. (greatly elevated). No such increases were seen in the breath of the control subject over the same period. An obvious positive correlation between breath carbon disulphide and acetone concentrations following disulfiram ingestion is seen and discussed.

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.

Brown LAS; Cook RT; Jerrells TR; Kolls JK; Nagy LE; Szabo G et al. Acute and chronic alcohol abuse modulate immunity. Alcoholism: Clinical and Experimental Research 30(9): 1624-1631, 2006. (43 refs.)

This article represents the proceedings of the Alcohol and Immunology Research Interest Group (AIRIG) meeting, a satellite workshop held at the 37th Annual Meeting of the Society for Leukocyte Biology. The meeting was sponsored by the AIRIG and the National Institute on Alcohol Abuse and Alcoholism. The presentations were as follows: (1) Effects of Ethanol on Immune Response to Hepatitis C Virus by Jack R. Wands, (2) Alcohol and Alveolar Macrophage Dysfunction: The Role of Chronic Oxidant Stress by Lou Ann S. Brown, (3) T Cell Responses to Listeria monocytogenes in Mice on a Chronic Ethanol Exposure Protocol by Robert T. Cook, (4) Mechanisms of Acute and Chronic Alcohol Consumption on Severity of Viral Infections by the Liver and Pancreas by Thomas R. Jerrells, (5) Acute and Chronic Effects on Macrophage Ectodomain Shedding: Implications for Lung Host Defenses by Jay K. Kolls, (6) Increased Susceptibility to Pseudomonas Infection of Burn-Injured Mice Given Alcohol Before Injury by Elizabeth J. Kovacs, (7) Regulation of Tumor Necrosis Factor alpha Expression in Macrophages by Chronic Ethanol by Laura E. Nagy, and (8) Hepatitis C Virus Infection and Alcohol Use by Gyongyi Szabo. Meeting coorganizers were Elizabeth J. Kovacs, Lou Ann S. Brown, Thomas R. Jerrells, and Robert T. Cook.

Brunelle C; Barrett SP; Pihl RO. Psychostimulant users are sensitive to the stimulant properties of alcohol as indexed by alcohol-induced cardiac reactivity. Psychology of Addictive Behaviors 20(4): 478-483, 2006. (48 refs.)

One indicator of increased sensitivity to alcohol-induced reward is a heightened heart rate (HR) increase following alcohol intoxication, I characteristic associated with increased alcohol-induced dopamine (DA) release. The goal of this study was to determine whether users of drugs known to induce DA release have higher HR increases after alcohol intoxication than never users have. Sixty-four men with known drug-use histories participated in an alcohol challenge in which HR was measured. Stimulant users had significantly higher ethanol-induced HR increases than never users had, although use of marijuana or hallucinogens was not associated with this marker. Stimulant users obtained superior Sensitivity to Reward scores (R. Torrubia, C. Avila, J. Molto, & X. Caseras, 2001) compared with never users. Stimulant drug users may be more sensitive to the stimulating properties of alcohol, and this appears to be mediated by superior activity in the Behavioral Approach System (J. A. Gray, 1991).

Bullers S; Ennis M. Effects of blood-alcohol concentration (BAC) feedback on BAC estimates over time. Journal of Alcohol and Drug Education 50(2): 66-87, 2006. (24 refs.)

This study examines the effects of self-tested blood alcohol concentration (BAC) feedback, from personal hand-held breathalyzers, on the accuracy of BAC estimation. Using an e-mail prompted web-based questionnaire, 19 participants were asked to report both BAC estimates and subsequently measured BAC levels over the course of 27 days. Results from the 14 subjects who reported drinking during that time period suggest that BAC estimation improves over the first four drinking events, only when controlling for amount of alcohol consumed. BAC estimate accuracy was found to decrease as number of drinks and measured BAC increased. Participants were more likely to over-estimate their BAC's than to under-estimate them but this trend was much more pronounced for light drinkers than for heavy drinkers. There were no additional effects of heavy/ light drinker status on estimate accuracy, beyond the effects of BAC at time of measured event.

Ceballos NA. Tobacco use, alcohol dependence, and cognitive performance. Journal of General Psychology 133(4): 375-388, 2006. (91 refs.)

Chronic alcohol abuse has long been associated with a mild, generalized pattern of cognitive decrements. However, it is important to note that problem drinking rarely occurs in isolation from abuse of other drugs. For people dependent upon alcohol, tobacco is one of the mostly commonly coabused substances. Recent research suggests that individuals with alcohol dependency may gravitate toward tobacco use, in part, because of the positive effects of nicotine on aspects of cognitive performance that may be compromised as a consequence of chronic alcohol misuse. In this article, the author focuses on the effects of nicotine on behavioral and electrophysiological indexes of cognitive performance, and the impact of these effects on alcohol-related cognitive decrements. The author discusses implications of these findings in the context of treatment and recovery of people with alcoholism.

Cook TAR; Wall TL. Ethnicity and the subjective effects of alcohol. IN: Earleywine M, ed. Mind-Altering Drugs: The Science of Subjective Experience. New York: Oxford University Press, 2005. pp. 154-182. (203 refs.)

It has been long recognized that there are differences between ethnic groups in rates of substance use and substance use disorders. It is recognized that genetic factors influence the subjective response to alcohol, with people having either a greater sensitivity, and there are those with a blunted response to alcohol. Liver enzymes involved in alcohol metabolism have been identified that are related to these effects. Research involving three ethnic groups -- Asians, Native Americans, and Jews. Rates of occurrence of different genetic variants impacting the response to alcohol are reviewed for these gorups. Of note is that while ethnicity may be considered as a single independent variable, this is not the case, and that formulation fails to to recognize the non-genetic factors, such as social and cultural factors, that also have a bearing on drinking practices.

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.

Danel T; Vantyghem M; Touitou Y. Responses of the steroid circadian system to alcohol in humans: Importance of the time and duration of intake. Chronobiology International 23(5): 1025-1034, 2006. (47 refs.)

Reports provide conflicting data about the effects of alcohol consumption on the hormonal system. Any study of these effects must control for a number of variables, including sex, alcohol status (alcoholic addiction vs. non-addiction), medical status (malnutrition, liver disease), and conditions of alcohol exposure, including an acute or continuous pattern of intake. The latter appears to be an especially critical factor in interpreting these effects. The authors therefore conducted a trial with a circadian design in which alcohol was administered repeatedly and regularly over a 26 h period for a total dose of 256 g. Because this protocol involves continuous alcohol administration, it is similar to administration among alcoholics and thus sheds new light on alcohol's effect on hormone secretion. Using healthy volunteers rather than alcoholics, however, prevents any confounding due to liver disorders and nutritional deficiencies, and thus makes it possible to focus on the direct role of alcohol in hormonal modifications. In these conditions, the continuous administration of alcohol did not affect cortisol secretion, but serum testosterone levels were significantly higher at all time points during the alcohol session than at the corresponding time points during the control session. These data are not consistent with previously reported findings for the relation between alcohol and both cortisol and testosterone, because in the current experiment the action of ethanol on steroid secretion should involve the circadian clock more than the hormonal system itself.

Davis TJ; de Fiebre CM. Alcohol's actions on neuronal nicotinic acetylcholine receptors. Alcohol Research and Health 29(3): 179-185, 2006. (31 refs.)

Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

Dick DM; Plunkett J; Wetherill LF; Xuei XL; Goate A; Hesselbrock V et al. Association between GABRA1 and drinking behaviors in the Collaborative Study on the Genetics of Alcoholism sample. Alcoholism: Clinical and Experimental Research 30(7): 1101-1110, 2006. (45 refs.)

Background: A wealth of literature supports the role of gamma-aminobutyric acid (GABA) in neurobiological pathways contributing to alcohol dependence and related phenotypes. Animal studies have consistently tied rodent homologs of the GABA(A) receptor genes on human chromosome 5q to alcohol-related behaviors; however, human studies have produced mixed results. Family-based association analyses previously conducted in the Collaborative Study on the Genetics of Alcoholism (COGA) sample yielded no evidence of association with Diagnostic and Statistical Manual of Mental Disorder-fourth edition (DSM-IV) alcohol dependence and these genes. As a follow-up to that study, we examined several alcohol-related behaviors in the COGA sample as follows: (1) a broader definition of alcohol dependence, including DSM-III-R symptoms and Feighner criteria (referred to as COGA alcohol dependence); (2) withdrawal; (3) history of alcohol-induced blackouts; (4) level of response to alcohol; (5) age of onset of regular drinking; and (6) age at first drunkenness. Methods: Family-based association tests were conducted, using multiple single-nucleotide polymorphisms (SNPs) in each of the 4 GABA(A) receptor genes on chromosome 5q. Results: In GABRA1, we found evidence of association with several of the drinking behavior phenotypes, including COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. We did not find consistent evidence of association with the remaining genes and any of the phenotypes. Conclusions: We found evidence for association between GABRA1 and COGA alcohol dependence, history of blackouts, age at first drunkenness, and level of response to alcohol. These analyses suggest that efforts to characterize genetic contributions to alcohol dependence may benefit by examining alcohol-related behaviors in addition to clinical alcohol dependence diagnoses.

Dickson PA; James MR; Heath AC; Montgomery GW; Martin NG; Whitfield JB et al. Effects of variation at the ALDH2 locus on alcohol metabolism, sensitivity, consumption, and dependence in Europeans. Alcoholism: Clinical and Experimental Research 30(7): 1093-1100, 2006. (40 refs.)

Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence.

Duranceaux NCE; Schuckit MA; Eng MY; Robinson SK; Carr LG; Wall TL. Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians. Alcoholism: Clinical and Experimental Research 30(9): 1470-1478, 2006. (77 refs.)

Background: Risk and protective factors for alcohol use disorders (AUDs) are complex and reflect both environmental and genetic factors. Genetic components account for about 50% of the variation and influence several phenotypes, including the level of response (LR) to alcohol as well as alcohol-metabolizing enzyme polymorphisms. Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations. Methods: This study evaluated associations of ADH1B and ADH1C genotypes in a non-Asian sample. Participants (N=117, 69.2% female) were 18- to 29-year-old men and women, primarily Caucasian (70.1%) and black (26.5%), recruited in San Diego, California. The Semi-Structured Assessment for the Genetics of Alcoholism Interview was used to assess demographic, substance use, and psychiatric history information, and the Family History Assessment Module was used to determine first-degree family history of alcohol dependence. An alcohol challenge paradigm was used to gather data on the LR to alcohol over 210 minutes. Results: Participants with the ADH1B(*)1/(*)2 genotype had a higher LR to alcohol early in the alcohol challenge (i.e., 30, 60, and 90 minutes after drinking) as measured by both alcohol-related changes in subjective feelings of intoxication and body sway, even when controlling for sex and Russian/Eastern European ancestry. A similar trend was seen for ADH1C(*)1/(*)1 genotype, although the results were not significant. Conclusions: These findings suggest that studies searching for genes relating to the LR to alcohol as a vulnerability factor for AUDs should consider controlling for ADH1B genotype, as the ADH1B(*)2 allele could obscure the impact of other genetic polymorphisms.

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.

Earleywine M, ed. Mind-Altering Drugs: The Science of Subjective Experience. New York: Oxford University Press, 2005. (Chapter refs.)

This edited volume in organized into 13 chapters and 20 contributors. The goal is to explore the subjective experience associated with substance use, the biological basis, and the implications for abuse potential. What is the nature of intoxication? This question is addressed in respect to hallucinogens, alcohol, opioids, marijuana, methylphenidate, and nitrous oxide. In addition there is examination of the relationship of ethnicity and acute effects for alcohol, the relationship of personality and the response to stimulant drugs, and interrelationship between sex and drugs.

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.

Feige B; Gann H; Brueck R; Hornyak M; Litsch S; Hohagen F et al. Effects of alcohol on polysomnographically recorded sleep in healthy subjects. Alcoholism: Clinical and Experimental Research 30(9): 1527-1537, 2006. (47 refs.)

Background: After studying the sleep of alcohol-dependent patients at the beginning and over the course of abstinence in earlier studies, our interest in the current study focused on the direct effect of 2 doses of alcohol [0.03 and 0.1% blood alcohol level (BAL)] on healthy sleep. This is the first polysomnographic study testing the impact of 2 doses of alcohol ingestion (thus reflecting "normal" social drinking and alcohol abuse) in a single-blind randomized design in healthy volunteers. The study evaluated a short-term acute drinking period for 3 and 2 days of withdrawal from alcohol not only for polysomnographic variables but also for subjective estimates of sleep quality. Mehods: In a crossover design with a 1-week interval, healthy subjects received alcohol to raise their blood alcohol to either 0.03 or 0.1% BAL at bedtime for 3 consecutive nights after an alcohol-free baseline night. Objective (polysomnography) and subjective sleep (questionnaires) was recorded each night. During the following 2 days, alcohol was discontinued with simultaneous measurements of sleep to gauge withdrawal effects. Results: At a dose of alcohol leading to BAL of 0.03%, no clear effects could be detected. Following an evening BAL of 0.1%, a hypnotic-like effect (shortened sleep latency, reduced number of wake periods, decreased stage 1 sleep) occurred primarily during the first half of the night with signs of rebound effects being already present during the second half of the night (increased stage 1 sleep). At this dose, alcohol significantly increased slow-wave sleep (SWS) in the first half of the night and reduced REM density in the beginning of the night. After discontinuation of the higher alcohol dose, REM sleep amount increased. No significant withdrawal or rebound effects could be observed for parameters of sleep continuity during the 2 nights after discontinuation from alcohol at a BAL of 0.1%. Conclusions: Owing to the small sample size, the results of this study need to be interpreted with caution. Short-term moderate alcohol consumption (BAL 0.03%) did not significantly alter objective or subjective parameters of sleep. Higher doses of alcohol resulting in a BAL level of 0.10% immediately before going to bed mainly influenced sleep in the first half of the night, resembling the effects of a short-acting hypnotic drug, including a suppression of phasic aspects of REM sleep (REM density). Interestingly, analysis of the latter part of these nights indicated the immediate presence of withdrawal effects (increased light sleep). No statistically significant effects on sleep parameters were observable during the 2 nights of withdrawal from alcohol at the higher BAL. Interpreted carefully, our data indicate that negative effects on sleep occur already with short-term use of alcohol at doses of BAL of 0.10%, despite hypnotic-like effects during the first hours of sleep, especially during the latter part of the night.

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.

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.

Galanter M, ed. Recent Developments in Alcoholism, Volume 17. Alcohol Problems in Adolescents and Young Adults: Epidemiology, Neurobiology, Prevention, Treatment. New York: Kluwer Academic/Plenum Press, 2005. (Chapter refs.)

The edited volume in the series "Recent Developments in Alcoholism" addresses teen drinking -- epidemiology, neurobiology, behavioral phenomena, diagnostic and assessment issues, prevention and treatment data -- in a developmental context. It is organized into four sections and includes 17 chapters and 50 contributors. In the first section on epidemiology, chapters deal with the initiation and course of alcohol use, those at risk for alcohol problems, as well as both acute and long-term problems. Section II on neurobiology considers the age-related effects, as well effects on memory, and phenomenon related to the fact that the adolescent brain is not fully matured. Section III on prevention contains chapters dealing with programs for specific populations, such as college students, and high risk groups, as well as an examination of policies to reduce underage drinking. In respect to treatment, attention is directed to co-occurring alcohol, drug and psychiatric disorders, cognitive-behavioral treatments, family therapy, and elements involved in assessment.

George WH; Davis KC; Norris J; Heiman JR; Schacht RL; Stoner SA et al. Alcohol and erectile response: The effects of high dosage in the context of demands to maximize sexual arousal. Experimental and Clinical Psychopharmacology 14(4): 461-470, 2006. (38 refs.)

Although drinking often precedes men's sexual activity, basic questions about alcohol's effects on men's sexual arousal remain unanswered. Inconsistencies in findings from studies examining subjective and physiological effects on erectile functioning suggest these effects are context specific, for example, dependent on whether a man wants to maximize or suppress his arousal. To address unresolved questions about alcohol and erectile functioning, the authors evaluated the effects of high blood alcohol concentrations (BACs) and arousal instructional demands on indices of penile circumference change and self-reported sexual arousal. In Study 1, a target BAC of 10% (vs..00%) attenuated peak circumference change from a neutral baseline but did not affect mean change, latency to arousal onset (a 5% increase in circumference from baseline), latency to peak achieved arousal, or subjective arousal, which correlated moderately with physiological indices. In Study 2, instructions to maximize (vs. suppress) arousal increased peak and mean circumference change and interacted with a target BAC of .08% (vs. .00%) to influence latency to arousal onset. Sober men instructed to maximize showed a shorter latency to arousal onset than did those instructed to suppress arousal; however, intoxicated men did not show a differential pattern. Moreover, compared with intoxicated counterparts, sober men instructed to maximize arousal showed a marginally shorter latency to arousal onset. Overall, alcohol and arousal instructions had small but discernible effects. Findings highlight the importance of contextual factors in alcohol's impact on erectile functioning.

Gerlach AL; Schiller A; Wild C; Rist F. Effects of alcohol on the processing of social threat-related stimuli in socially phobic women. British Journal of Clinical Psychology 45(Part 3): 279-295, 2006. (68 refs.)

Background. Social phobics are at a higher risk of developing alcohol problems. The mechanism promoting this association is not clear. According to Sayette (I 993b), alcohol attenuates anxiety responses by disrupting initial appraisal of threatening stimuli. We used the emotional Stroop test and an implicit memory test to investigate whether alcohol hinders appraisal of social threat words in patients diagnosed w, ith social phobia. Procedure. Thirty-two women with social phobia (DSM-IV) and 32 female controls performed an emotional Stroop test either after drinking alcohol resulting in a blood alcohol levels (BAL) of 0.6%. or after drinking a non-alcoholic beverage. The emotional Stroop test contained social anxiety-related and neutral stimuli. Implicit memory for the words presented was tested with a word-stem completion test. Results. Without alcohol, both controls and socially-phobic participants took longer to name the colour of socially-threatening stimuli than of neutral stimuli. Alcohol levelled response latencies to the two stimulus categories only in controls. Socially-phobic participants responded more slowly to social anxiety-related stimuli than to neutral stimuli, irrespective of their BAL. In contrast to controls, social phobics showed an implicit memory bias for social threat words. This bias was attenuated by alcohol. Discussion. Alcohol disrupts appraisal of social anxiety-related stimuli in controls but not in social phobics; in these it hinders the consolidation of memory. This also suggests that social phobics experience similar anxiety with and without alcohol, but remember this experienced anxiety less precisely. This effect might act as a reinforcer for the use of alcohol for the purpose of self-medication in future situations.

Giancola PR. Influence of subjective intoxication, breath alcohol concentration, and expectancies on the alcohol-aggression relation. Alcoholism: Clinical and Experimental Research 30(5): 844-850, 2006. (54 refs.)

Background: The purpose of this study was to investigate the influence of subjective intoxication, alcohol-aggression expectancies, and breath alcohol concentration (BrAC) on intoxicated aggression in men and women while controlling for dispositional aggressivity. Methods: Subjects were 328 (163 men and 165 women) healthy social drinkers between 21 and 35 years of age. Following the consumption or either an alcohol or an active placebo beverage, subjects were tested on a modified version of the Taylor Aggression Paradigm in which mild electric shocks were received from, and administered to, a fictitious opponent during a competitive task. Levels of subjective intoxication and BrAC were measured immediately before subjects began the aggression task, Aggressive behavior was operationalized as the shock intensities administered to the fictitious opponent under conditions of low and high provocation. Results: Subjective intoxication ratings were not related to aggressive behavior for either men or women. Alcohol-aggression expectancies were related to aggression for men, but this effect was rendered nonsignificant when controlling for dispositional aggressivity, which in turn, was significantly related to the dependent variables for both men and women. Finally, BrAC was also related to aggression above and beyond the effects of dispositional aggressivity, yet only for men. Conclusions: Taken as a whole, this study suggests that intoxicated aggression is primarily the result of alcohol's pharmacological properties in conjunction with an aggressive disposition.

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.

Graham AW; Schultz TK; Mayo-Smith MF; Ries RK; Wilford BB, eds. Principles of Addiction Medicine. Chevy Chase MD: American Society of Addiction Medicine, 2003. (Chapter refs.)

This volume is a comprehensive text on addictions. It is organized into 14 major sections, each of which has multiple chapters. There are over 200 contributors. The sections deal with the following themes: basic science and core concepts; pharmcology; diagnosis, assessment and early intervention; overview of addiction treatment; management of intoxication and withdrawal; pharmacologic interventions; behavioral interventions; 12-step programs and other recovery-oriented interventions; alcohol and drug problems in the workplace; medical disorders and complications of addiction; co-occurring addictive and psychiatric disorders; pain and addiction; and children and adolescents. There are also six appendices.

Graham K; Osgood DW; Wells S; Stockwell T. To what extent is intoxication associated with aggression in bars? A multilevel analysis. Journal of Studies on Alcohol 67(3): 382-390, 2006. (30 refs.)

Objective: The purpose of this study was to assess the relationship between level of intoxication and the frequency and severity of aggression at the person, incident, visit, and bar level for aggressive incidents observed in bars or clubs. Method: Hierarchical Linear Modeling (HLM) analysis of 1,025 incidents of aggression documented by trained observers during 1,334 nights of observation in 118 bars and clubs in Toronto, Canada, was conducted. Results: Both level of intoxication of the crowd during the visit as well as mean level of intoxication at the bar level significantly predicted frequency of aggression. There was a positive association between level of intoxication and severity of aggression at both the incident and person level except for the highest level of intoxication at the person level, where severity of aggression was less than for moderate intoxication. A person-incident level interaction between intoxication and severity of aggression was also found. Conclusions: These results suggest that prevention efforts should focus on both identifying bars that typically have more intoxicated patrons and reducing the intoxication levels of patrons across bars generally. The results also showed a strong positive relationship between level of intoxication and severity of aggression (except at the highest levels), indicating that intoxication increases risk in terms of both frequency and severity of aggression. The significant interaction between person- and visit-level intoxication suggests that greater attention needs to be paid to group dynamics in alcohol-related aggression.

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.

Heilig M; Egli M. Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms. (review). Pharmacology & Therapeutics 111(3): 855-876, 2006. (218 refs.)

Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CBI receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients.

Hermann D; Smolka MN; Wrase J; Klein S; Nikitopoulos J; Georgi A et al. Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI. Alcoholism: Clinical and Experimental Research 30(8): 1349-1354, 2006. (35 refs.)

Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D-2/3 blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.

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.

Hinckers AS; Laucht M; Schmidt MH; Mann KF; Schumann G; Schuckit MA et al. Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents. Biological Psychiatry 60(3): 282-287, 2006. (46 refs.)

Background. A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-H7-T) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. Methods: Data were extracted from a subset (h = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. Results: The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p =.005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. Conclusions: This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.

Hughes JR. Should criteria for drug dependence differ across drugs? Addiction 101(Supplement 1): 134-141, 2006. (77 refs.)

Aim: To examine the pros and cons of using the same diagnostic criteria for dependence across all drugs versus using dependence criteria specific to the drug of interest. Methods: A qualitative review of the similarities and differences in nicotine versus alcohol and opiate dependence is used as an example of the utility of using generic versus drug-specific criteria. Results: Many scientists implicitly recognize that nicotine dependence is different when they do not include nicotine dependence when studying 'drug dependence'. Nicotine and alcohol/opiate dependence have many similarities (e.g. both can cause withdrawal). Among the several differences, the most important is that nicotine dependence does not cause acute behavioral impairment. Some of the generic dependence criteria do not apply to nicotine dependence (e.g. giving up activities to use the drug) and some well-validated measures of nicotine dependence (e.g. time to first cigarette) are not included in the generic criteria. Conclusion: Empirical tests of the relative utility of generic versus drug-specific criteria are needed.

Kasuda S; Sakurai Y; Shima M; Morimura Y; Kudo R; Takeda T et al. Inhibition of PAR4 signaling mediates ethanol-induced attenuation of platelet function in vitro. Alcoholism: Clinical and Experimental Research 30(9): 1608-1614, 2006. (36 refs.)

Background: Reduction in coronary heart disease morbidity in response to moderate consumption of alcoholic beverages may be partly mediated by ethanol-induced inhibition of platelet function. However, the precise mechanisms by which ethanol modulates platelet activation induced by thrombin, which plays a central role in hemostasis, remain unclear. The goal of this study was to investigate ethanol-induced changes in platelet function and clarify the underlying mechanisms including PAR1 and PAR4 activity and [Ca2+](i) dynamics in vitro. Methods: Platelet aggregation, increase in intracellular calcium ([Ca2+](i)), and release of platelet factor 4 and beta-thromboglobulin induced by alpha-thrombin, PAR1-agonist peptide (AP), or PAR4-AP were assessed in the presence or absence of ethanol. Results: Ethanol exposure inhibited low-dose thrombin (0.5 nM)-induced aggregation but not an increase in [Ca2+](i). In contrast, ethanol had no effect on high-dose thrombin (10 nM)-induced aggregation or the [Ca2+](i) increase. Ethanol did not significantly inhibit thrombin-induced release of platelet factor 4 and beta-thromboglobulin. Ethanol reduced PAR1-AP-induced aggregation, but did not affect the spike form of [Ca2+](i) increase. In contrast, ethanol inhibited the increase in [Ca2+](i) as well as the aggregation in response to PAR4-AP and resulted in delayed [Ca2+](i) peak time. Furthermore, ethanol inhibited both PAR1-AP- and PAR4-AP-induced platelet factor 4 and beta-thromboglobulin release. Conclusions: These data suggest that ethanol inhibits platelet aggregation via inhibition of PAR4 signaling and subsequent inhibition of Ca2+ influx and granule release. This phenomenon may contribute to the reduction in coronary heart disease morbidity in response to consumption of alcoholic beverages.

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.

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.

Kinney J. Loosening the Grip. A Handbook of Alcohol Information. 8th edition. New York: McGraw-Hill, 2006. (Chapter refs.)

This is the eighth edition of a handbook on alcohol use and alcohol problems. The book examines the full range of psychological factors, physiological effects, prevention strategies, treatment options, and family concerns related to substance abuse, focusing on alcohol as one of the most commonly used substances. The chapters deal with (1) history of alcohol use; (2) problems resulting from alcohol and other drug use; (3) acute effects of alcohol on the body; (4) the nature and course of alcohol dependence; (5) etiology, in terms of genetic, psychological, and environmental factors; (6) medical complications (7) behavioral aspects of alcohol dependence; (8) family issues; (9) evaluation and treatment; (10) special populations; (11) psychiatric considerations; (12) other drugs use, by drug class, with information of desired effects, acute effects, chronic effects, use patters, and types and patterns; and (13) professional principles and issues. Appendices include a list of North American substance abuse field organizations, a table presenting alcohol's interaction with other drugs, and online Internet resources for educators.

Kirchner TR; Sayette MA; Cohn JF; Moreland RL; Levine JM. Effects of alcohol on group formation among male social drinkers. Journal of Studies on Alcohol 67(5): 785-793, 2006. (56 refs.)

Objective: Social factors affect alcohol use and misuse, but researchers rarely study the acute effects of alcohol in groups. This study used systematic observation techniques to measure the effects of alcohol on behavioral responses during an initial group interaction. Method: Fifty-four male social drinkers were assembled into three-person groups of mangers, and all members of each group were administered either a 0.82 g/kg dose of alcohol or a placebo to be consumed during a 30-minute period. This social interaction was video recorded, Objective: Social factors affect alcohol use and misuse, ye researchers rarely study the acute effects of alcohol in groups. This study used systematic observation techniques to measure the effects of alcohol on behavioral responses during an initial group interaction. Method: Fifty-four male social drinkers were assembled into three-person groups of mangers, and all members of each group were administered either a 0.82 g/kg dose of alcohol or a placebo to be consumed during a 30-minute period. This social interaction was video recorded,and the duration and sequence of selected smiling and speech behaviors were coded on a 1-second time base. Results: Alcohol consumption increased individual- and group-level coordination of smiling and speech behaviors over time and improved self-reported bonding. Conclusions: These data suggest that alcohol may facilitate social bonding during initial group formation. Measuring behavioral responses in a social context provides new directions for studying the acute effects of alcohol.

Koob GF; Le Moal M. Neurobiology of Addiction. New York: Academic Press, 2005. (Chapter refs.)

This volume is intended to provide a current survey and synthesis of the important findings in the understanding of neurobiological mechanisms of addiction over the past 50 years. Following an introduction outlining the nature of addiciton, attention turns to descriptions of animal models of addiction. The next five chapters describe the neurobiological mechanisms of addiction for psychostimulants, opioids, alcohol, nicotine and cannabinoids. For each drug class there is discussion of the history and use of the drug, its sources, the pharmacokinetics, the associated psychopathology for drugs in that class, as well as the behavioral and neurobiological mechanism of action at the molecular, cellular and neurocircuitry level of analysis. There is also a chapter on neuroimaging and drug addiction. The final chapters examine theories of addiction at the neurobiological and neuroadaptational level both from a historical and integrative perspective.

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.

Lane SD; Yechiam E; Busemeyer JR. Application of a computational decision model to examine acute drug effects on human risk taking. Experimental and Clinical Psychopharmacology 14(2): 254-264, 2006. (60 refs.)

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Buserneyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

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.

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.

Marczinski CA; Fillmore MT. Clubgoers and their trendy cocktails: Implications of mixing caffeine into alcohol on information processing and subjective reports of intoxication. Experimental and Clinical Psychopharmacology 14(4): 450-458, 2006. (46 refs.)

Alcoholic drink preferences in college students have made an interesting shift recently, with trends in consumption leaning toward caffeinated alcohol in various forms (e.g., Red Bull and vodka or caffeinated beers such as Anheuser-Busch's B-to-the-E). Despite the dramatic rise in popularity of these beverages, little research has examined the combined effects of alcohol and caffeine, which is problematic for adequately informing the public about the risk or lack thereof of these drinks. The purpose of this study was to directly investigate the acute effects of alcohol and caffeine, alone and in combination, on well-validated measures of cognitive performance and subjective intoxication in social drinkers. Participants (N = 12) performed a psychological refractory period task that measured dual-task interference as the prolonged reaction time to complete the 2nd of 2 tasks performed in close temporal sequence. Performance was tested under 2 active doses and 1 placebo dose of caffeine (0.0 mg/kg, 2.0 mg/kg, and 4.0 mg/kg) in combination with I active dose and 1 placebo dose of alcohol (0.0 g/kg and 0.65 g/kg). As expected, alcohol impaired task performance by increasing dual-task interference and increasing errors. The coadministration of caffeine counteracted the effects of alcohol on interference but had no effect on the degree to which alcohol increased errors. Subjective measures of intoxication showed that coadministration of caffeine with alcohol reduced participants' perceptions of alcohol intoxication compared with administration of alcohol alone. The results highlight the complexity of drug interactions between alcohol and caffeine.

Martin CS; Balaban CD; McBurney DH. Tonic and phasic processes in the acute effects of alcohol. Experimental and Clinical Psychopharmacology 14(2): 209-218, 2006. (30 refs.)

This article presents a novel method for measuring the acute effects of alcohol. One hundred twenty nonproblem drinkers aged 21-28 participated in 3 alcohol administration sessions that produced peak blood alcohol concentrations (BACs) near .09 g%. Subjective intoxication ratings were taken at multiple points across rising and falling BACs. Mathematical modeling techniques decomposed intoxication ratings into a tonic component sensitive to BAC level and a phasic component sensitive to BAC rate of change. This model provided a good fit to observed data. Tonic and phasic gain parameters showed high repeatability across sessions. The average phasic gain parameter was about 4 times larger than the average tonic gain parameter, indicating that subjective intoxication is usually more affected by BAC change than by BAC level. The associations of drinking practices with tonic and phasic gain parameters varied by gender and family history of alcoholism. Tonic-phasic modeling allows individual and group differences in the acute effects of alcohol to be studied as time-dynamic processes.

Mennella JA; Pepino MY. Short-term effects of alcohol consumption on the hormonal milieu and mood states in nulliparous women. Alcohol 38(1): 29-36, 2006. (49 refs.)

The present study was designed to determine the short-term effects of alcohol consumption on hormonal responses and mood states in nulliparous women who have regular menstrual cycles. To this aim, we conducted a within-subjects design study in which eight women consumed a 0.4-g/kg dose of alcohol in orange juice during one test session (alcohol condition) and an equal volume of orange juice (control condition) during the other. Changes in plasma prolactin, oxytocin and cortisol levels, blood alcohol concentrations (BACs), and mood states were compared. BAC peaked at approximately 36.7 + 5.4 min after the consumption of the alcoholic beverage and decreased thereafter. Alcohol consumption significantly increased the area under the concentration-time curve (AUC) of prolactin (P < .01) and decreased the oxytocin AUC (P = .04) when compared to the control condition. Cortisol AUCs were not different across the two experimental conditions. Similar to that previously observed in lactating women, changes in prolactin and oxytocin paralleled changes in feelings of drunkenness. The magnitude and persistence of the alcohol-induced hormonal changes in nulliparous women were significantly less pronounced than those observed in lactating women, further highlighting the dynamics of the system under study during lactation.

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.

Papamichael C; Karatzi K; Karatzis E; Papaioannou TG; Katsichti P; Zampelas A et al. Combined acute effects of red wine consumption and cigarette smoking on haemodynamics of young smokers. Journal of Hypertension 24(7): 1287-1292, 2006. (30 refs.)

OBJECTIVE: Red wine seems to improve haemodynamic variables, while smoking provokes adverse effects. The haemodynamic effects of their combined use is unknown. The purpose of the present study was to examine the acute effects of red wine and its constituents, in combination with the smoking of one cigarette, on haemodynamic parameters, such as blood pressure and wave reflections, in a group of smokers. METHODS: Twenty smokers (12 males, eight females) participated in a double-blind, crossover study comprised of 3 study days. All subjects either smoked one cigarette, or smoked and drank 250 ml of red wine, or 250 ml of de-alcoholized red wine (containing the same type and similar concentration of antioxidants). Applanation tonometry and generalized transfer functions were used to estimate aortic pressure waveforms at baseline and 30, 60 and 90 min after each trial. The augmentation index (AIx) was used to express wave reflections. RESULTS: Smoking increased peripheral systolic blood pressure (P < 0.005) 30 min later, but simultaneous consumption of either type of red wine caused no such effect. Additionally, smoking caused no overall effect on AIx, while smoking and drinking either regular or de-alcoholized red wine reduced AIx (P < 0.001). The reduction of AIx after red wine consumption was significantly greater than the respective reduction after de-alcoholized red wine (P = 0.004). CONCLUSION: Antioxidant substances in red wine counteracted the smoking-induced increase in peripheral systolic blood pressure. Both alcohol and antioxidants in red wine decrease wave reflections in uncomplicated habitual smokers postprandially, indicating an additional favourable effect of red wine.

Parrott A; Morinan A; Moss M; Scholey A. Understanding Drugs and Behaviour. Chichester: John Wiley & Sons, 2004

This book is intended to explicate the effects of drugs on behaviour, mood, cognition, sensation, awareness, health and well-being. This volume is organized into four parts. Part I deals with drug and their actions, with attention to how the major psychoactive drugs alter brain chemistry, and the role of neurotransmitters. Part II considers the non-medical use of psychoactive drugs. Individual chapters are devoted to the central nervous system stimulants, nicotine, LSD, ecstasy, marijuana, heroin and opiates, central nervous system depressants, and alcohol and drug dependence. Part III turns to clinical and medical use of psychoactive drugs: the antipsychotics, antidepressants and mood stabilizers, and cognitive enhancers. Part IV provides a summary.

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.

Paulus MP; Tapert SF; Pulido C; Schuckit MA. Alcohol attenuates load-related activation during a working memory task: Relation to level of response to alcohol. Alcoholism: Clinical and Experimental Research 30(8): 1363-1371, 2006. (53 refs.)

A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level-dependent activation to an event-related visual working memory test was examined. The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load-dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Low-level responders relative to high-level responders exhibited an increased working memory load-dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol.

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.

Pruett BS; Pruett SB. An explanation for the paradoxical induction and suppression of an acute phase response by ethanol. Alcohol 39(2): 105-110, 2006. (31 refs.)

Binge ethanol (EtOH) consumption suppresses inflammatory responses and resistance to infection, but paradoxically it is associated with increased levels of acute phase proteins (which are indicators of inflammation) and an increased risk of inflammation-mediated pathologies such as cardiovascular disease and cirrhosis of the liver. The latter effect may be mediated by increased translocation of bacteria leading to activation of toll-like receptor 4 (TLR4). In this study, the dose-response and time course of the effects of EtOH alone or EtOH in conjunction with a TLR4 agonist (lipopolysaccharide [LPS]) were evaluated in mice. EtOH alone at a dosage of 6 g/kg induced an acute phase response (as indicated by enzyme-linked immunosorbent assay for serum amyloid A and serum amyloid P) that was maximal 24 h after dosing. Lower dosages of EtOH did not have this effect but did suppress the acute phase response to LPS and the production of interleukin-6 up to 3 h after dosing. EtOH at 6 g/kg did not induce an acute phase response in C3H/HeJ (TLR4 mutant) mice, indicating that this response is mediated through TLR4. These results provide a resolution for the apparently paradoxical pro- and anti-inflammatory actions of EtOH with regard to acute phase responses.

Ray LA; McGeary J; Marshall E; Hutchison KE. Risk factors for alcohol misuse: Examining heart rate reactivity to alcohol, alcohol sensitivity, and personality constructs. Addictive Behaviors 31(11): 1959-1973, 2006. (31 refs.)

Objective: Heart rate reactivity to alcohol has been conceptualized as an index of alcohol-induced reward and has been associated with a sensation seeking personality profile. The goal of this study is to expand on previous findings regarding the significance of heart rate reactivity to alcohol while examining convergent lines of research on alcohol sensitivity, the rewarding effects of alcohol, and personality constructs. Methods: Participants (N = 47) were heavy drinkers who completed an intravenous alcohol challenge protocol. Results: Analyses revealed a significant negative relationship between heart rate reactivity and alcohol-induced sedation and subjective intoxication. Heart rate reactivity was positively related to self-reported alcohol-induced vigor and to impulsivity and sensation seeking scores. Conclusions: Taken together, these results suggest that individuals with heightened heart rate reactivity to alcohol appear to be more sensitive to the invigorating properties of alcohol, while being less sensitive to the sedative and unpleasant effects of alcohol intoxication. These findings have implications to the conceptualization of heart rate reactivity to alcohol as a biobehavioral marker of alcohol sensitivity.

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.

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.

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 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; Pierson J; Danko GP; Beltran IA. Relationships among the level of response to alcohol and the number of alcoholic relatives in predicting alcohol-related outcomes. Alcoholism: Clinical and Experimental Research 30(8): 1308-1314, 2006. (39 refs.)

The low level of response (LR) to alcohol is related to a family history (FH) of alcohol use disorders (AUDs), and each predicts alcohol-related outcomes. Few studies have evaluated the interrelationships between the number of alcoholic relatives, LR, and a range of alcohol-related outcomes. This study tests the hypotheses that there will be an inverse relationship between LR and FH and that LR will be a better predictor of the maximum quantity of alcohol consumed. Data were extracted from personal interviews with 376 males from 20 years of follow-up in the San Diego Prospective Study. Level of response had been established at about age 20 through alcohol challenges in this population, about half of whom had at least one alcoholic relative. Face-to-face follow-ups with both the subjects and additional informants were carried out 10, 15, and 20 years later. These analyses used correlations and regressions to evaluate the relationship between the 2 major predictors (FH and LR) and 5 alcohol-related outcomes over 20 years of follow-up. As predicted, the alcohol challenge-based LR correlated significantly with the number of alcoholic relatives (up to -0.17 for subjects with clearly high and low LR scores). Each of the 2 predictors correlated with the 5 outcomes, including the maximum quantity of alcohol consumed since original testing, maximum frequency, nondiagnostic alcohol-related problems, the number of 11 DSM-IV (Fourth Diagnostic and Statistical Manual of Mental Disorders) abuse and dependence items, and having developed alcohol abuse or dependence. In hierarchical regression analyses, LR contributed significantly to the prediction of all 5 outcomes, even when considered in the context of FH, with only LR predicting drinking quantity and frequency, but both items adding to the prediction of alcohol-related problems and diagnoses. These results were not affected by the intensity of usual drinking when LR had been measured at age 20. Both FH and LR contributed to a range of alcohol-related outcomes, with LR alone significantly predicting maximum quantity and frequency in regression analyses.

Schuckit MA; Smith TL; Waylen A; Horwood J; Danko GP; Hibbeln JR et al. An evaluation of the performance of the self-rating of the effects of alcohol questionnaire in 12-and 35-year-old subjects. Journal of Studies on Alcohol 67(6): 841-850, 2006. (60 refs.)

Objective: A low level of response (LR) to alcohol was originally established through evidence of less alcohol-related change in several parameters at a given blood alcohol level. This is a genetically influenced phenotype associated with an increased risk for alcoholism. When measured by a retrospective questionnaire (the Self-Rating of the Effects of Alcohol [SRE] scale), a lower LR (here indicated by a report that more drinks were historically needed for various effects) correlates with a family history of alcoholism and numerous alcohol use-related variables. The current analyses address the questions of how higher SRE scores (as indicators of a low LR) relate to alcohol use and problems across different age groups and when considered in the context of demography (e.g., age, gender, and weight), as well as the number of items endorsed on the questionnaire. Method: SRE data (scores and numbers of items endorsed), demography, and alcohol-related variables (quantity, frequency, and problems) were evaluated in two populations. The first population included 334 12-year-old children from the Avon Longitudinal Study of Parents and Children, and the second included more than 400 35-year-old men from the San Diego Prospective Study. In each group, Pearson correlations were established among all variables, and items that were significantly linked to alcohol-related outcomes were entered into regression analyses as predictors of these outcomes. Results: In both samples, SRE scores correlated with all alcohol-related outcomes, with the highest values for the maximum quantity of alcohol consumed. Relationships between the SRE score and alcohol-related variables remained robust in both populations when entered into regression analyses incorporating demography and the number of SRE items answered by subjects. Conclusions: The SRE score appears to perform relatively similarly across the two populations regarding relationships with alcohol quantity, frequency, and problems. The most consistent results were observed for the maximum quantity of alcohol consumed.

Schulteis G; Liu J. Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats. Alcohol 39(1): 21-28, 2006. (57 refs.)

Withdrawal from an acute bolus injection of ethanol produces affective or emotional signs that include anxiogenic-like behavior and conditioned place aversion. This study assessed whether brain reward deficits that accompany withdrawal from chronic ethanol dependence are also observed upon withdrawal from acute intoxication. Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle in the lateral hypothalamus and trained on a discrete-trial current-intensity brain stimulation reward threshold paradigm. Ethanol intoxication was produced by bolus intraperitoneal injections of ethanol (1.0, 1.5, or 2.0 g/kg). Brain reward thresholds were monitored periodically following the bolus injection (3, 6, 9, 12, 24, 48, 72, 96 h postethanol). Blood samples taken at various intervals postethanol revealed that peak blood alcohol levels (BAL) at all doses tested were reached within 10 min of injection. Following doses of 1.0, 1.5, and 2.0 g/kg ethanol, BAL had declined to undetectable levels within 3-6 h postinjection. Withdrawal from a single injection of ethanol resulted in a significant but transient increase in brain reward thresholds only with the highest ethanol dose tested (2.0 g/kg). When acute intoxication and withdrawal episodes were repeated two additional times at weekly intervals, the peak magnitude and duration of threshold elevation increased significantly at the 2.0 g/kg dose of ethanol. A significant but transient increase in thresholds was also seen in the group treated with 1.5 g/kg ethanol during the third and final week of testing. Results indicate that withdrawal from a single exposure to an intoxicating dose of ethanol produces significant brain reward deficits in addition to other affective disturbances previously reported, and that repeated weekly intoxication and withdrawal results in a progressive increase in magnitude and duration of the reward deficit.

Sher KJ; Wood MD. Subjective effects of alcohol. Part II. IN: Earleywine M, ed. Mind-Altering Drugs: The Science of Subjective Experience. New York: Oxford University Press, 2005. pp. 135-153. (124 refs.)

This chapter is the second of two dealing with alcohol. The focus is upon individual differences as influences and factors in determining the subjective effects of alcohol. Two domains are reviewed. One is genetics, aspects addressed include a family history of alcoholism, the effects on stressed and non-stressed individuals, and candidate genes. Personality is the other domain considered, with discussion of personality traits such as impulsivity, alcohol expectancies, cognitive functioning,