Alcohol and Alcoholism - current issue

Introduction to the Special Issue of Alcohol and Alcoholism on Sex/Gender Differences in Responses to Alcohol

Devaud, L. L., Prendergast, M. A. — Wed, 21 Oct 2009 07:24:33 PDT

The Influence of Chronic Nicotine Administration on Behavioural and Neurochemical Parameters in Male and Female Rats after Repeated Binge Drinking Exposure

Lallemand, F., Ward, R. J., De Witte, P. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: The possible interaction between nicotine and ‘binge drinking’ in eliciting changes in behavioural patterns of ‘binge drinking’ rats as well as nucleus accumbens (NAc) glutamate levels has been investigated in these present studies. Methods: Adult or adolescent male and female rats received ethanol, 2 g/kg or 3 g/kg, by gavage in a ‘binge drinking’ regimen (3 times/day over a 6 h period, for 2 days followed by 5 days of abstinence) combined with or without nicotine, 0.3 g/kg, for either a 5-week (adult) or a 4-week (adolescent) period. Motor activity was then assessed for a period of 60 min after three further doses of ethanol or water. In addition, the NAc glutamate level was assayed in each group for 1 h after the first gavage regimen with ethanol, 2 g/kg or 3 g/kg, or water. Results: Adult female rats showed greater sensitivity to each ethanol dose (2 g/kg and 3 g/kg) than the adult male rats, their motor activity decreasing during the first and third ‘binge’. In contrast, in male adult rats, the sedative effects of ethanol were reduced, particularly after the third binge when no significant changes in the locomotor activity were apparent between the ethanol-administered male rats and controls. Adolescent rats did differ in their response to ethanol in comparison with adult rats. It was noteworthy that in young female adolescent rats, given 2 g/kg ethanol, motor activity was enhanced, thereby indicating that adolescent female rats are less sensitive to the sedative effects of ethanol at specific doses. In addition, male and female adolescent rats showed little change in locomotor activity in comparison with controls during the third ‘binge administration’ possibly indicating that tolerance to such alcohol doses was occurring. Nicotine administration did prevent the decrease in locomotor activity after ethanol administration during the first binge regimen in both male and female adolescents as well as adult female rats. However, after the third binge, such alcohol-induced changes in motor activity were not so well defined in the female adult rats that now showed significant decreases in motor activity. In contrast, adolescent male and female rats still showed similar motor activity to that of the controls. No clear association between the NAc glutamate extracellular content and locomotor activity was discernible in either adult or adolescent rats in these present studies. However, chronic nicotine administration markedly reduced the elevated basal glutamate content in the ‘binge drinking female’ adult rats. Conclusions: These studies have shown clear and distinct differences, with respect to both sensitivity and tolerance, in adult and adolescent male and female rats, which could be modified by supplementation with nicotine.

Sex Differences in Ethanol Intake and Sensitivity to Aversive Effects during Adolescence and Adulthood

Vetter-O'Hagen, C., Varlinskaya, E., Spear, L. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: The present experiments examined sex differences in ethanol intake and in the influence of a social context on aversive properties of ethanol in adolescent and adult Sprague-Dawley rats. Methods: Experiment 1 examined ethanol intake, with animals receiving daily 2-h access to ethanol and water for 8 days. Experiment 2 assessed the aversive effects of ethanol using a conditioned taste aversion (CTA) paradigm, with animals placed either alone or with a same-sex, same-age peer during the ethanol intoxication phase of conditioning. Results: Ethanol intake varied with both age and sex, although the sex differences emerging at each age were opposite in nature. Adolescent males consumed more ethanol relative to their body weights than adolescent females and adults of both sexes, whereas adult females generally consumed more than adult males. The CTA test revealed no sex differences in aversive effects of ethanol in adults, whereas adolescent males were less sensitive to the aversive properties of ethanol than adolescent females when intoxication occurred in the presence of a peer. Ethanol-induced CTA was evident in adults at lower doses than in adolescents. Conclusions: These results suggest that age differences in ethanol intake in males and sex differences in intake during adolescence may be associated in part with the relative insensitivity of the male adolescents to ethanol's aversive properties, especially when intoxication occurred in a social context. However, the elevated ethanol intake observed in adult females relative to their male counterparts appears to be unrelated to the aversive properties of ethanol.

Sexually Dimorphic Effects of Alcohol Exposure during Development on the Processing of Social Cues

Kelly, S. J., Leggett, D. C., Cronise, K. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: The study used an animal model of fetal alcohol spectrum disorders (FASD) to investigate the impact of alcohol exposure during a period equivalent to all three trimesters in humans on social recognition memory. It was hypothesized that the effects on specific aspects of social recognition memory would be sexually dimorphic. Methods: This study exposed rats to ethanol during both the prenatal and early postnatal periods. Two control groups included a group exposed to the administration procedures but not ethanol and a non-treated group. At ~90 days, all rats were tested repeatedly in a test of social recognition memory with a juvenile animal of the same sex. Experimental rats of both sexes were allowed to investigate an unknown juvenile for either 2, 3 or 5 min and then, after a delay of 30, 60, 120 and 180 min, were allowed to investigate the same juvenile for 5 min. Results: Male rats investigated the juvenile for much longer than female rats. Ethanol-exposed male rats showed a deficit in recognition memory that was evident with longer delays when the initial investigation time was either 2- or 3-min long. In contrast, ethanol-exposed female rats showed a deficit in recognition memory only when the initial investigation period was of 2 min. Measurement of oxytocin receptor binding in the amygdala region indicated that ethanol exposure lowered oxytocin receptor binding in females but not males. Conclusions: The results suggest that ethanol exposure during development caused a deficit in memory duration but not encoding in males and a deficit in encoding but not memory duration in females. The deficit in ethanol-exposed females may be related to changes in oxytocin receptors in the amygdala.

Sex Differences in Acoustic Startle Responses and Seizure Thresholds between Ethanol-Withdrawn Male and Female Rats

Reilly, W., Koirala, B., Devaud, L. L. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: We have found consistent and significant sex differences in recovery from the increased seizure susceptibility observed during ethanol withdrawal (EW) in our rat model system. The main objective of the present study was to determine if sex differences in EW generalized to an additional behavioral measure startle reactivity. Methods: Acoustic startle or seizure threshold responses were measured in separate groups of rats at 1 day or 3 days of EW. Results: Both pair-fed control and EW males showed greater increases in acoustic startle responses than either the female or ovariectomized female (OVX) counterparts. There was a selective effect of pregnanolone on acoustic startle in that it reduced peak force of response only at 3 days EW in male rats. Unexpectedly, it modestly increased startle reactivity in control female and OVX rats. Acute treatment with low-dose ethanol trended toward reducing startle responses in control animals, as expected, while generally enhancing startle responses during EW. All sex conditions showed an enhanced startle response during EW following administration of the higher dose of estradiol compared to control animals. Estradiol did not alter seizure thresholds in control animals. However, it was anticonvulsant for males at 3 days EW, females and OVX at 1 day EW. Conclusions: Observed sex differences in the startle reactivity during EW were consistent with earlier findings comparing EW seizure risk in male and female rats. Responses of OVX suggested that both hormones and differences in brain structures between males and females have a role in these sex differences. Our findings add weight to recommendations that treatment of alcohol withdrawal in humans should consider hormonal status as well as withdrawal time.

Sex Differences in Caffeine Neurotoxicity Following Chronic Ethanol Exposure and Withdrawal

Wed, 21 Oct 2009 07:24:33 PDT

Aims: Caffeine is a central nervous system stimulant that produces its primary effects via antagonism of the A₁ and A_2A adenosine receptor subtypes. Previous work demonstrated a sex difference in neurotoxicity produced by specific adenosine A₁ receptor antagonism during ethanol withdrawal (EWD) in vitro that was attributable to effects downstream of A₁ receptors at NMDA receptors. The current studies were designed to examine the effect of non-specific adenosine receptor antagonism with caffeine during ethanol withdrawal on hippocampal toxicity in cultures derived from male and female rats. Methods: At 5 days in vitro (DIV), half of the male and female organotypic hippocampal slice cultures were exposed to 50 mM ethanol (EtOH) in culture media for 10 days before exposure to caffeine (5, 20 and 100 µM) for the duration of a 24 h EWD period. In keeping with this timeline, the remaining ethanol-naïve cultures were given media changes at 10 and 15 DIV and exposed to caffeine (5, 20 and 100 µM) for 24 h at 15 DIV. Cytotoxicity was assessed by fluorescent microscopy and quantification of propidium iodide (PI) uptake in the pyramidal cell layers of the CA1 and CA3 regions and the granule cell layer of the dentate gyrus (DG). A two-way (sex x treatment) ANOVA was conducted within each hippocampal region. Results: Twenty-four-hour withdrawal from 10-day exposure to 50 mM ethanol did not produce increased PI uptake in any hippocampal region. Caffeine exposure (5, 20 and 100 µM) in ethanol-naïve cultures did not produce toxicity in the DG or CA1 region, but 20 µM caffeine produced modest toxicity in the CA3 region. Exposure to 20 µM caffeine during EWD produced cytotoxicity in all hippocampal regions, though toxicity was sex-dependent in the DG and CA1 region. In the DG, both 5 and 20 µM caffeine produced significantly greater PI uptake in ethanol-exposed female cultures compared to ethanol-naïve female cultures and all male cultures. Similarly, 20 µM caffeine caused markedly greater toxicity in female cultures as compared to male cultures in the CA1 region. Conclusions: Twenty-four-hour exposure to caffeine during EWD produced significant toxicity in the pyramidal cell layer of the CA3 region in male and female cultures, though toxicity in the granule cell layer of the DG and pyramidal cell layer of the CA1 region was observed only in female cultures. Greater sensitivity of the female slice cultures to toxicity upon caffeine exposure after prolonged ethanol exposure is consistent with previous studies of effects of a specific A₁ receptor antagonism during EWD on toxicity and indicate that this effect is independent of the hormonal milieu. Together, these data suggest that the A₁ receptor subtype is predominant in mediating caffeine's neurotoxic effects during EWD. These findings demonstrate the importance of considering gender/sex when examining neuroadaptive changes in response to ethanol exposure and withdrawal.

Sex-Specific Dissociations in Autonomic and HPA Responses to Stress and Cues in Alcohol-Dependent Patients with Cocaine Abuse

Wed, 21 Oct 2009 07:24:33 PDT

Aims: Chronic alcohol and drug dependence leads to neuroadaptations in hypothalamic–pituitary–adrenal (HPA) and sympathetic adrenal medullary (SAM) stress systems, which impact response sensitivity to stress and alcohol cue and facilitates risk of relapse. To date, gender variations in these systems have not been fully assessed in abstinent alcohol-dependent individuals who also met criteria for cocaine abuse. Methods: Forty-two (21 M/21 F) early abstinent treatment-seeking substance-abusing (SA) men and women and 42 (21 M/21 F) healthy control (HC) volunteers were exposed to three 5-min guided imagery conditions (stress, alcohol/drug cue, neutral relaxing), presented randomly, one per day across three consecutive days. Alcohol craving and anxiety ratings were obtained as well as measures of heart rate (HR), blood pressure, plasma ACTH, cortisol, norepinephrine (NE) and epinephrine (EPI). Results: SA males showed increased ACTH and EPI basal tone compared with HC males and SA females. However, they demonstrated no increase in ACTH and cortisol levels following stress and alcohol cue imagery exposure compared to the neutral condition. SA females demonstrated a typically increased stress response in both measures. In addition, SA males showed no increase in cardiovascular response to either stress or cue, and no increase in catecholamine response to cue compared with their response to neutral imagery. Again, this dampening was not observed in HC males who produced significantly higher levels of cue-related HR and EPI, and significantly higher stress-related DBP. In contrast, SA females showed an enhanced ACTH and cortisol response to stress and cue compared with neutral imagery and this was not observed in the HC females. They also demonstrated a reduced increase in NE and EPI compared with both SA males and HC females as well as reduced HR compared with HC females. Conclusions: While SA males showed a generalized suppression of HPA, SAM system and cardiovascular markers following both stress and cue, SA women demonstrated a selective sympatho-adrenal suppression to stress only and an enhanced HPA response to both stress and cue. These gender variations are discussed in terms of their potential impact on relapse vulnerability and treatment outcome.

Gender Differences in Alcohol Impairment of Simulated Driving Performance and Driving-Related Skills

Miller, M. A., Weafer, J., Fillmore, M. T. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: Considerable laboratory research indicates that moderate doses of alcohol impair a broad range of skilled activities related to driving performance in young adults. Although laboratory studies show that the intensity of impairment is generally dependent on the blood alcohol concentration, some reviews of this literature suggest that women might be more sensitive to the impairing effects of alcohol than men. The present study tested this hypothesis. Methods: Drawing on data from previous experiments in our laboratory, we compared men and women in terms of the degree to which a challenge dose of alcohol (0.65 g/kg) impaired their simulated driving performance and measures of three separate behavioral and cognitive functions important to driving performance: motor coordination, speed of information processing and information-processing capacity. Results: Alcohol significantly impaired all aspects of performance. Moreover, women displayed greater impairment than men on all behavioral tests and also reported higher levels of subjective intoxication compared with men. Conclusions: Both biological and social–cultural factors have been implicated in gender differences in the behavioral responses to alcohol. The current evidence of heightened sensitivity to alcohol in women highlights the need for better understanding the biological and environmental factors underlying this gender difference.

Sex Differences in NMDA Receptor Expression in Human Alcoholics

Ridge, J. P., Ho, A. M.-C., Dodd, P. R. — Wed, 21 Oct 2009 07:24:33 PDT

Aim: The aim of this study was to assess whether chronic alcohol misuse affects N-methyl-d-aspartate (NMDA) receptor subunit concentrations in human cases, and whether male and female subjects respond differently. Methods: Real-time RT-PCR normalized to GAPDH was used to assay NR1, NR2A and NR2B subunit mRNA in superior frontal (SFC) and primary motor (PMC) cortex tissue obtained at autopsy from chronic alcoholics with and without comorbid cirrhosis of the liver, and from matched controls. Results: The expression of all three subunits was significantly lower in both areas of cirrhotic alcoholics than in either controls or alcoholics without comorbid disease, who did not differ significantly. Values were also influenced by the subject's sex and genotype. The µ-opiate receptor C1031G polymorphism selectively modulated NMDA transcript expression in cirrhotic-alcoholic SFC, an effect that was more marked for NR1 and NR2A than for NR2B subunit transcripts. Contrasting 5HT1B genotypes affected NMDA mRNA expression differently in male and female SFC, but not PMC, in cirrhotic alcoholics. Conclusion: NMDA receptor subunit expression may differentially influence male and female cirrhotic alcoholics’ susceptibility to brain damage.

Introduction: Gendering Socio Cultural Alcohol and Drug Research

Hensing, G., Spak, F. — Wed, 21 Oct 2009 07:24:33 PDT

Aim: The gender gap in alcohol consumption and alcohol-related harm still is considerable and largely unexplained. This paper introduces four studies performed in Sweden that explore factors influencing gender differences in levels of consumption, adverse consequences and treatment. Method: We summarize and discuss these four studies performed within the same cultural setting, which each analyse interaction with the gender. Results: Two studies focus on the individual level addressing criminal behaviour, alcohol problems and mortality, and gender identity and alcohol problems in women taking psychiatric co-morbidity into account. Two studies focus on the institutional and cultural levels addressing the handling of alcohol-related problems in primary healthcare and the effectiveness of using cultural analysis in identifying gender concerns for women. Conclusion: Future studies need to focus more on these complex associations to secure that treatment settings provide both genders with fair and adequate treatment of high quality and that prevention activities will start to test measures that take gender into consideration.

Alcohol Use and Patterns of Delinquent Behaviour in Male and Female Adolescents

Eklund, J. M., af Klinteberg, B. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: The overall aim was to study patterns of delinquent behaviour in relation to adolescent alcohol use. The more specific aims were to examine whether alcohol use varied between groups of adolescents with different patterns of delinquent behaviour, and to explore whether the association between delinquent behaviour patterns and alcohol use was similar for males and females. Methods: The participants were male (n = 406) and female (n = 532) adolescents in the eighth grade (age 14 years) in a medium-sized city of Sweden. We used information about self-rated alcohol use and different types of delinquent behaviour. Results: The results revealed that the occurrence of excessive alcohol use and drunkenness varied between groups of adolescents with different delinquency patterns, and that the associations between alcohol use and patterns of delinquent behaviours were relatively similar for males and females. Adolescents with patterns characterized by more serious non-violent delinquency or by violent delinquency reported the highest occurrence of alcohol use and frequency of drunkenness. Adolescents with well-adjusted behaviour or occasional minor delinquency were less likely to report drinking large amounts of alcohol or to the point of feeling drunk. Conclusions: The present results further emphasize the importance of distinguishing between different offender groups when examining the relationship between delinquent behaviour and associated problems, such as excessive alcohol use.

Cultural Analysis as a Perspective for Gender-Informed Alcohol Treatment Research in a Swedish Context

DeMarinis, V., Scheffel-Birath, C., Hansagi, H. — Wed, 21 Oct 2009 07:24:33 PDT

Aim: An exploratory study to investigate the role of culture in women's drinking at a clinic for women with alcohol problems in a Swedish treatment context. Methods: A content analysis of the case journal material of 20 consecutive female patients at the EWA clinic (Early treatment of Women with Alcohol addiction) in Stockholm, Sweden, was conducted using an original instrument informed by the field of cultural psychiatry and emerging from recurrent themes in the case journals. Results: The patients perceived themselves as having a sub-group status. A trajectory of ritualized actions around drinking, especially private drinking rituals, was identified. Existential components of patients’ struggles with addiction in a highly secularized cultural context were identified. Multiple, contradictory explanatory frameworks for understanding drinking problems were creating cognitive dissonance. Conclusion: Using cultural analysis as a perspective for gaining gendered information may allow for identifying new patterns within specific cultural and subgroup contexts. It may contribute new information to the following treatment research areas: gender-appropriate measurement issues; service integration; gender-appropriate services for women; and, drinking rituals and patterns.

Does Gender Matter? A Vignette Study of General Practitioners' Management Skills in Handling Patients with Alcohol-Related Problems

Geirsson, M., Hensing, G., Spak, F. — Wed, 21 Oct 2009 07:24:33 PDT

Aims: The aims of this study were to analyse the perceptions of female and male primary care physicians (PCPs) of alcohol problems in male and female patients, their recommendations to reduce or abstain from alcohol, their referrals to treatment and their views of safe levels of drinking for male and female patients. These factors were related to the physicians’ own alcohol consumption. Methods: A slightly adjusted version of the WHO Collaborative Study Questionnaire for General Practitioners was posted to all PCPs (n = 132) in the district of Skaraborg, Sweden, of whom 68 PCPs responded. In the questionnaire, the PCPs’ perceptions of two patient vignettes were analysed. Results: Both the gender of the patients in the vignettes and of the PCPs influenced the advice and the referrals that the patients received: 83% of male excessive drinkers and 47% of female excessive drinkers were recommended to cut down on drinking. In 50% of cases, the male excessive drinker was not referred, compared with 25% for the female excessive drinker. This was statistically significant only for excessive drinkers. The odds ratio for referral to any treatment was 0.33 (CI = 0.12–0.93) for the male excessive drinker compared with the female excessive drinker. The male PCP referred the excessive drinker less often to any treatment than did the female PCP, odds ratio 0.26 (CI = 0.08–0.90). The upper limit of alcohol consumption before the PCPs would advise the patient to cut down was significantly higher for PCPs with the AUDIT-C score ≥ 3. The limit was 146 g/week for male patients and 103 g/week for female patients. Corresponding figures for PCP with the AUDIT-C score ≤ 2 were 89 and 68 g/week. Conclusion: Male patients were less likely to be advised to stop drinking altogether than female patients and were less likely to be referred, according to this vignette study. Taking into account that male patients have a higher prevalence of alcohol problems, this may be of considerable importance for men's health outcomes. Implications of these findings are the need to increase awareness of male excessive drinking and that gendered perceptions might bias alcohol management recommendations.

Lack of Leadership Confidence Relates to Problem Drinking in Women: Gender Identity, Heavy Episodic Drinking and Alcohol Use Disorders in Swedish Women

Hensing, G., Spak, F. — Wed, 21 Oct 2009 07:24:33 PDT

Aim: The aim of this study was to analyse in women the association between four dimensions of gender identity, heavy episodic drinking (HED) and alcohol use disorders (AUD), taking into account age, personality, psychiatric co-morbidity and level of education. Methods: An initial screening of alcohol consumption was followed by a structured psychiatric interview in a sample of women drawn from the Gothenburg population and women attending primary care, maternity and hospital services (n = 930). Gender identity was assessed using the Masculinity–Femininity Questionnaire (M/F-Q) (items grouped into four dimensions: leadership, caring, self-assertiveness and emotionality). The Karolinska Scale of Personality was administered. Clinical psychiatric diagnoses according to DSM were made in face-to-face interviews. HED was defined as consumption of at least 60 g of ethanol on a single day at least once a month. Results: Women who scored low on the leadership dimension were twice as likely to have AUD [age-adjusted odds1.98 (95% confidence interval 1.30–3.01)] compared to those with medium scores. These odds ratios were significant after adjustment for personality [2.21 (1.35–3.63)], psychiatric disorders [2.09 (1.25–3.47)] and level of education [1.95 (1.17–3.26)]. Low scores on the leadership dimension were associated with HED [1.55 (0.98–2.44)] after adjustment for age, personality, psychiatric disorders and level of education. High scores on leadership were not significantly associated with AUD or HED after these adjustments. The odds ratios for those who scored low on caring were non-significant throughout the analyses of associations with both AUD and HED. A similar pattern was found for the self-assertiveness dimension. Low emotionality was associated with decreased odds for AUD [0.42 (0.25–0.70)] and HED [0.66 (0.44–0.99)], and increased odds for AUD [2.14 (1.38–3.31)] and HED [2.33 (1.58–3.44)], after adjusting for age. These associations became non-significant after adjustment for personality and remained so after psychiatric disorders and level of education were added to the models. Conclusion: Of the four gender identity dimensions, only low scores on leadership remained significantly associated with AUD and HED after adjustment for age and personality. Clinical work could focus on the development of leadership abilities in women scoring low on these items to improve the ability.

Biomarkers for Detecting Thiamine Deficiency--Improving Confidence and Taking a Comprehensive History Are Also Important

Immadisetty, V., Cant, T., Thyarappa, P., Lingford-Hughes, A., Vernon, J. — Wed, 21 Oct 2009 07:24:33 PDT

The Cure for Alcoholism. Drink Your Way Sober without Willpower, Abstinence or Discomfort

Beaglehole, A. — Wed, 21 Oct 2009 07:24:33 PDT

Alcohol and Human Health

Paton, A. — Wed, 21 Oct 2009 07:24:33 PDT

Relapse Prevention--Maintenance Strategies in the Treatment of Addictive Behaviour (2nd Edition)

Ritson, B. — Wed, 21 Oct 2009 07:24:33 PDT

Raising the Bar--Preventing Aggression in and around Bars, Pubs and Clubs

Plant, M. — Wed, 21 Oct 2009 07:24:33 PDT