Gender differences in pharmacokinetics of alcohol

BACKGROUND: The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated. METHODS: Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione-dependent formaldehyde dehydrogenase). RESULTS: Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric chi-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects. CONCLUSIONS: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.     

Further evidence of an inverse genetic relationship between innate differences in alcohol preference and alcohol withdrawal magnitude in multiple selectively bred rat lines

Background: We have previously shown that a genetic association exists between low alcohol drinking and high alcohol withdrawal magnitude after acute alcohol exposure in alcohol‐naïve rats. However, the behavioral rating scale used in this prior study was not optimal for assessing the magnitude of mild alcohol withdrawal. The present study examined whether a genetic relationship is again found between alcohol preference and alcohol withdrawal magnitude when a sensitive measure is used to index mild alcohol withdrawal in rats. Methods: Alcohol‐naïve, male rats selectively bred for alcohol preference (P, HAD1, HAD2) or nonpreference (NP, LAD1, LAD2) received a single intragastric infusion of alcohol (4.0 g/20.3 ml/kg body weight; 25% v/v) or water followed by acoustic startle testing. Results: Startle probability and magnitude was greater in water‐treated P than in water‐treated NP rats. During alcohol withdrawal, startle probability and magnitude was suppressed in P rats and elevated in NP rats relative to water‐treated controls. Startle probability and magnitude was greater in water‐treated LAD1 rats than in water‐treated HAD1 rats. During alcohol withdrawal, startle probability and magnitude was suppressed in HAD1 and elevated in LAD1 rats relative to water‐treated controls at 20 hr after acute alcohol exposure. Startle probability and magnitude did not differ between water‐treated HAD2 and water‐treated LAD2 rats. During alcohol withdrawal, there was a trend toward decreased startle probability and magnitude in HAD2 rats compared with water‐treated controls. Conclusions: The acoustic startle response to a tone stimulus is a sensitive measure of mild alcohol withdrawal in rats. Rats selectively bred for low alcohol intake showed greater alcohol withdrawal magnitude than did rats selectively bred for high alcohol intake. These results provide further evidence that an inverse genetic association exists between alcohol withdrawal magnitude and propensity toward alcohol drinking in rats.     

The association between alcohol consumption patterns and adherence to food consumption guidelines

Objective: To examine the association between alcohol consumption patterns and adherence to major food consumption guidelines in adults in Spain. Methods: Telephone survey of 12,037 persons, representative of the population age 18 to 64 years in the region of Madrid, conducted from 2000 to 2005. The threshold between average moderate and excessive drinking was 40 g alcohol/d in men and 24 g/d in women. Binge drinking was defined as intake of ≥80 g alcohol in men and ≥60 g in women during 1 drinking session in the last 30 days. Food consumption was measured with a 24‐hour recall. Statistical analyses were performed using logistic regression and adjusted for the main confounders. Results: In total, 4.3% of study participants were excessive drinkers and 10.3% binge drinkers; 6.5% preferred spirits and 24.2% drank with meals. In comparison with never drinking, average moderate drinking with binge drinking was associated with excessive meat consumption (>1 serving/d). Excessive alcohol consumption without binge drinking was associated with insufficient intake of milk products (<2 servings/d) and excessive consumption of meat, fish, and eggs (>2 servings/d). Excessive drinkers with binge drinking more often did not meet the guidelines on consumption of fruit and vegetables (<3 servings/d), milk products, and meat. Excessive drinkers, with and without binge drinking, were more likely to skip a meal, especially breakfast. Consumption mainly of spirits was associated with insufficient fruit and vegetable consumption, and with skipping a meal. Finally, drinking at mealtimes was associated with poor adherence to most of the food consumption guidelines. No dietary differences between men and women were found in relation to alcohol consumption. Conclusions: Average excessive alcohol consumption, binge drinking, preference for spirits, and drinking alcohol at mealtimes are associated with poor adherence to major food consumption guidelines.     

Alcohol consumption before and during pregnancy comparing concurrent and retrospective reports

BACKGROUND: Reported alcohol consumption during pregnancy has proven to be higher when reported retrospectively during or after the pregnancy, compared with concurrent reports. In a longitudinal, population-based questionnaire study, we investigated whether these findings could be replicated. METHODS: A longitudinal, population-based questionnaire study. Among a representative half of pregnant women in Oslo, 92% accepted to join the study. Non-Norwegian speaking and/or immigrants from nonwestern countries were not invited. Questionnaires were answered at 17 (T1) and 30 weeks of pregnancy (T2) and 6 months after term (T3). The response rate was at T1 93% (N = 1,749), at T2 82%, and at T3 94% [representing 86% (T1), 70% (T2), and 64% of those invited to join the study]. RESULTS: Significantly more alcohol consumption after pregnancy recognition was reported retrospectively at both T2 and T3 [T2 0.15 and T3 0.18 standard units per week (SU/wk)] than concurrently at T1 or T2 (T1 0.10 and T2 0.14 SU/wk). When comparing the 2 retrospective reports at T2 and T3, there was a significant increase over time. Predictive factors for higher retrospective reports were higher age, more SU per week before pregnancy, reported alcohol use after pregnancy recognition (at T1), and depression after the pregnancy. A predictive factor for lower retrospective reporting was anxiety during, but not after, the pregnancy. Contrary to previous suggestions, anxiety concerning abnormality in the 6-month-old child was not a predictive factor. CONCLUSION: Concurrently reported alcohol consumption during pregnancy is probably under-reported. Thus, concurrent reports appear to underestimate fetal exposure.     

Exploring pregnancy-related changes in alcohol consumption between black and white women

Background: Although epidemiological data indicate that White women are more likely to drink and binge drink before pregnancy, fetal alcohol syndrome (FAS) is more common in the Black population than among Whites in the United States. Differences in drinking cessation between Black and White women who become pregnant may help explain the disparity in FAS rates. Methods: The study sample was comprised of 280,126 non‐Hispanic Black and White women, ages 18 to 44, from the Behavioral Risk Factor Surveillance System (BRFSS) 2001 to 2005 data sets. Predictors of reduction in alcohol consumption (in drinks per month) and binge drinking (>4 drinks on one occasion) by pregnant and non‐pregnant women were identified with logistic regression. The effect of interactions of pregnancy status with age, education, and Black or White race on drinks per month and binge occasions were explored using analysis of variance (ANOVA). Results: Pregnant White women averaged 79.5% fewer drinks per month than non‐pregnant White women (F = 1250.1, p < 0.001), and 85.4% fewer binge drinking occasions (F = 376, p < 0.001). Pregnant Black women averaged 58.2% fewer drinks per month than non‐pregnant Black women (F = 31.8, p < 0.001) and 64.0% fewer binge occasions (F = 13.8, p < 0.001). Compared to Black women, White women appear to make a 38% greater reduction in drinks per month, and a 33% greater reduction in binge occasions. Conclusions: Non‐Hispanic White women appear more likely to reduce drinks per month and binge drinking occasions than non‐Hispanic Black women during pregnancy. These findings may help explain disparities in FAS in the United States, though this cross‐sectional sample does not permit claims of causation. To better describe the impact of differential drinking reduction on FAS rates, future studies of longitudinal data should be done.     

Maximum quantity consumed and alcohol-related problems: assessing the most alcohol drunk with two measures

PURPOSES: The maximum amount of alcohol consumed on any day is an important indicator of problem drinking. This study examined the ability of 2 maximum measures, taken individually and in combination, to predict alcohol-related consequences and dependence symptoms. METHOD: We analyzed data from 4,296 current drinkers who participated in the 2000 National Alcohol Survey (N10) and provided complete data on several alcohol measures. Items included the most they drank in any day in the past 12 months assessed by 2 questions: a standard question with a 6-level categorical response format and an open-ended (continuous) question referencing the occasion that you had the most to drink that followed items on drinking contexts. RESULTS: In a within-subjects analysis, more than two-thirds of the respondents provided consistent responses on both questions (69.9%), 12.4% respondents reported higher maximum quantities on the open-ended question partitioned into equivalent categories, and 17.7% reported a higher maximum on the initial categorical question. In multiple logistic regression analyses predicting alcohol-related consequences, the continuous open-ended maximum or the mean of the 2 maximum items were the strongest predictors, whereas for predicting alcohol dependence symptoms, the maximum of the open-ended and closed-ended maximum items was a better predictor than each measure alone. CONCLUSION: Although categorical response formats generally capture high-quantity drinking better than open-ended formats, use of a second, alternatively formatted "most drunk" question may modestly improve ability to predict survey indicators of alcohol use disorders.     

Translation of an evidence-based social skills intervention for children with prenatal alcohol exposure in a community mental health setting

Background: Children with prenatal alcohol exposure (PAE) have significant social skills deficits and are often treated in community mental health settings. However, it remains unclear whether these children can be effectively treated using manualized, evidence‐based interventions that have been designed for more general mental health populations. Methods: To shed light on this issue, the effectiveness of Children’s Friendship Training (CFT) versus Standard of Care (SOC) was assessed for 85 children ages 6 to 12 years with and without PAE in a community mental health center. Results: Children participating in CFT showed significantly improved knowledge of appropriate social skills, improved self‐concept, and improvements in parent‐reported social skills compared to children in the SOC condition. Moreover, results revealed that within the CFT condition, children with PAE performed as well as children without PAE. Findings indicated that CFT, an evidence‐based social skills intervention, yielded greater gains than a community SOC social skills intervention and was equally effective for children with PAE as for those without PAE. Conclusions: Results suggest that children with PAE can benefit from treatments initiated in community settings in which therapists are trained to understand their unique developmental needs, and that they can be successfully integrated into treatment protocols that include children without PAE.     

Alcohol consumption and problems: the relevance of drinking patterns

BACKGROUND: Data on risks and benefits associated with drinking patterns provide the scientific basis for moderate, low-risk drinking guidelines. Illustrated are methods to investigate and adjust for heterogeneity in relations between three-dimensional drinking patterns and 41 alcohol problems assessed among current regular drinkers in the 1988 National Health Interview Survey. METHODS: Three dimensions of mean drinking patterns, (i.e., usual quantities, heavy drinking rates (days of 5+ drinks/drinking days x 100), and drinking frequencies) were estimated in overlapping subsets of the population reporting each of the 41 problems, and mean usual quantities and heavy drinking rates were plotted against frequencies. Respondents were categorized into drinking problem groups associated with comparable mean drinking patterns; and main and interactive effects of age and sex on drinking patterns were examined by conducting three regression analyses within each group, with quantity, frequency, and heavy drinking rates as dependent variables, respectively. RESULTS: Analyses revealed substantial heterogeneity in relations between drinking patterns and alcohol problems. Respondents having only minor problems drank on average two days a week, usually had 2.6 drinks, and drank heavily 12-13 days a year. Whereas, those having minor and severe problems drank an average of 3.5 days a week, usually had 4.7 drinks, and drank heavily 58 days a year. Within each problem group, usual quantity and frequency were higher among males than females, but the greatest gender differences were seen in heavy-drinking rates. Age-related differences in drinking patterns were striking. Usual quantity and heavy-drinking rates associated with problems decreased with age, whereas drinking frequency increased. CONCLUSIONS: Findings demonstrated the importance of assessing and adjusting for heterogeneity in relations between drinking patterns and alcohol problems when aggregating and interpreting such data, (e.g., when assessing alcohol dependence criteria or evaluating guidelines for moderate drinking), and illustrated new methods for doing so.     

老年人健康行为与心理健康关系的调查

目的探讨老年人的健康行为与心理健康之间的关系。方法采用候玉波等编制的健康行为量表和症状自评量表（SCL-90）对300名老年人进行测试,并进行相关分析。结果不同年龄和文化程度老年人在健康行为与心理健康方面有显著性差异（P〈0.05）;参与活动与心理健康水平呈显著正相关（P〈0.05）;心理应激、不良生活习惯与心理健康呈显著负相关（P〈0.05）。结论积极参与各项活动、减少各种心理应激和建立良好的生活习惯有利于提高老年人的心理健康水平。     

The relationship between recent alcohol use and sexual behaviors: gender differences among sexually transmitted disease clinic patients

Background: Binge drinking is associated with risky sexual behaviors and sexually transmitted diseases (STDs). Few studies have investigated this by gender or in an STD clinic. This cross‐sectional study examined the association between binge drinking and risky sexual behaviors/STDs among patients attending an urban STD clinic. Method: A total of 671 STD clinic patients were tested for STDs, and queried about recent alcohol/drug use and risky sexual behaviors using audio computer‐assisted‐self‐interview. The association between binge drinking and sexual behaviors/STDs was analyzed using logistic regression adjusting for age, employment, and drug use. Results: Binge drinking was reported by 30% of women and 42% of men. Gender differences were found in rates of receptive anal sex which increased linearly with increased alcohol use among women but did not differ among men. Within gender analyses showed that women binge drinkers engaged in anal sex at more than twice the rate of women who drank alcohol without binges (33.3% vs. 15.9%; p < 0.05) and 3 times the rate of women who abstained from alcohol (11.1%; p < 0.05). Having multiple sex partners was more than twice as common among women binge drinkers than women abstainers (40.5% vs. 16.8%; p < 0.05). Gonorrhea was nearly 5 times higher among women binge drinkers compared to women abstainers (10.6% vs. 2.2%; p < 0.05). The association between binge drinking and sexual behaviors/gonorrhea remained after controlling for drug use. Among men, rates of risky sexual behaviors/STDs were high, but did not differ by alcohol use. Conclusion: Rates of binge drinking among STD clinic patients were high. Among women, binge drinking was uniquely associated with risky sexual behaviors and an STD diagnosis. Our findings support the need to routinely screen for binge drinking as part of clinical care in STD clinics. Women binge drinkers, in particular, may benefit from interventions that jointly address binge drinking and risky sexual behaviors. Developing gender‐specific interventions could improve overall health outcomes in this population.     

Missed opportunities in addressing drinking behavior in medical and mental health services

BACKGROUND: Epidemiological and clinical literature point to the importance of screening for alcohol problems in medical and psychiatric settings. However, little is known about which problem drinkers seek help from those services or about the characteristics of those who have their drinking addressed. METHODS: We interviewed a probability sample of adult dependent and problem drinkers in the general population (n = 672) and consecutive admissions to chemical dependency programs in a northern California county (n = 926). We reinterviewed them 1 year later and measured medical and mental health visits and whether their drinking was addressed during the visit. RESULTS: Almost two-thirds of problem drinkers had a medical visit, and approximately one-third had a mental health visit, yet drinking was not often discussed, especially during medical visits. Many of those more likely to have a visit were not more likely to have their drinking addressed. Women and individuals older than 40 years had more medical and mental health visits [odds ratio (OR), 1.71; p < 0.001 and OR, 1.55; p < 0.001, respectively, for women; OR, 1.57; p < 0.05 and OR, 1.64; p < 0.05, respectively, for age >/=40 years], but were not more likely to have their drinking addressed in either setting, and women were less likely than men to have their drinking addressed in mental health settings (OR, 0.62; p < 0.05). Those with higher alcohol severity and those who had attended chemical dependency treatment during the previous year were more likely to have their drinking addressed in each setting. Insurance status predicted medical, but not mental health, visits and was not related to having drinking addressed in either setting. CONCLUSIONS: Drinking behavior was not routinely addressed by medical and mental health practitioners for dependent and problem-drinking men and women who presented in public and private medical and mental health settings.     

Mood and implicit alcohol expectancy processes: predicting alcohol consumption in the laboratory

Background: Implicit positive alcohol expectancy (PAE) processes are thought to respond phasically to external and internal stimuli—including mood states—and so they may exert powerful proximal influences over drinking behavior. Although social learning theory contends that mood states activate mood‐congruent implicit PAEs, which in turn lead to alcohol use, there is a dearth of experimental research examining this mediation model relative to observable drinking. Moreover, an expectancy theory perspective might suggest that, rather than influencing PAEs directly, mood may moderate the association between PAEs and drinking. To test these models, this study examined the role of mood in the association between implicitly measured PAE processes (i.e., latency to endorse PAEs) and immediate alcohol consumption in the laboratory. Gender differences in these processes also were examined. Method: College students (N = 146) were exposed to either a positive, negative, or neutral mood induction procedure, completed a computerized PAE reaction time (RT) task, and subsequently consumed alcohol ad libitum. Results: The mood manipulation had no direct effects on drinking in the laboratory, making the mediation hypothesis irrelevant. Instead, gender and mood condition moderated the association between RT to endorse PAEs and drinking in the laboratory. For males, RT to tension reduction PAEs was a stronger predictor of volume of beer consumed and peak blood alcohol concentration in the context of general arousal (i.e., positive and negative mood) relative to neutral mood. RT to PAEs did not predict drinking in the laboratory for females. Conclusions: The results show that PAE processes are important determinants of immediate drinking behavior in men, suggesting that biased attention to mood‐relevant PAEs—as indicated by longer RTs—predicts greater alcohol consumption in the appropriate mood context. The findings also highlight the need to consider gender differences in PAE processes. This study underscores the need for interventions that target automatic cognitive processes related to alcohol use.     

The relationship between patterns of alcohol use and mental and physical health disorders in two American Indian populations

AIMS: First, define alcohol use categories among two reservation-based American Indian (AI) populations based on the relationship between alcohol consumption and dependence. Secondly, examine associations between the alcohol use categories and other indicators of health status. DESIGN, PARTICIPANTS AND MEASUREMENTS: Epidemiological data on 1287 AIs aged 18-57 years who consumed alcohol during the past year. CHAID tree analysis, a hierarchical partitioning method, was used to analyze alcohol quantity (highest number of drinks consumed during 1 day) and frequency (number of days drank during the past month) data to define quantity-frequency categories distinguished by differing rates of alcohol dependence. Multivariate analyses assessed relationships between the alcohol use categories thus identified and a number of health outcomes. FINDINGS: People who reported drinking 12 or more drinks during 1 day and more than 4 days a month had the highest prevalence of alcohol dependence. Among the males who drank > 18 drinks the prevalence was 42.12% and among females who drank 12 or more drinks, 44.58%. The prevalence among males who drank > 18 drinks yet drank less frequently was also high (24.06%). Although findings differed by gender, drinkers in the highest risk category for alcohol dependence were most likely to report drug use disorders, mood/anxiety disorders, alcohol-related physical disorders and lower quality of life. CONCLUSIONS: The quantity thresholds defined to identify AIs at highest risk for alcohol dependence in this study differed by gender and were higher than typically reported for non-AIs. They are consistent with previous findings regarding the pattern of high-quantity, low-frequency alcohol consumption among AIs residing on reservations.     

Gender differences in the performance of a computerized version of the alcohol use disorders identification test in subcritically injured patients who are admitted to the emergency department

OBJECTIVE: The Alcohol Use Disorder Identification Test (AUDIT) has been recommended as a screening tool to detect patients who are appropriate candidates for brief, preventive alcohol interventions. Lower AUDIT cutoff scores have been proposed for women; however, the appropriate value remains unknown. The primary purpose of this study was to determine the optimal AUDIT cutpoint for detecting alcohol problems in subcritically injured male and female patients who are treated in the emergency department (ED). An additional purpose of the study was to determine whether computerized screening for alcohol problems is feasible in this setting. METHODS: The study was performed in the ED of a large, urban university teaching hospital. During an 8-month period, 1205 male and 722 female injured patients were screened using an interactive computerized lifestyle assessment that included the AUDIT as an embedded component. World Health Organization criteria were used to define alcohol dependence and harmful drinking. World Health Organization criteria for excessive consumption were used to define high-risk drinking. The ability of the AUDIT to classify appropriately male and female patients as having one of these three conditions was the primary outcome measure. RESULTS: Criteria for any alcohol use disorder were present in 17.5% of men and 6.8% of women. The overall accuracy of the AUDIT was good to excellent. At a specificity >0.80, sensitivity was 0.75 for men using a cutoff of 8 points and 0.84 for women using a cutoff of 5 points. Eighty-five percent of patients completed computerized screening without the need for additional help. CONCLUSIONS: Different AUDIT scoring thresholds for men and women are required to achieve comparable sensitivity and specificity when using the AUDIT to screen injured patients in the ED. Computerized AUDIT administration is feasible and may help to overcome time limitations that may compromise screening in this busy clinical environment.     

Effects of alcohol consumption on the allergen-specific immune response in mice

Background:  There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization.
Objective:  To investigate the effects of alcohol consumption on the allergen-specific immune response in mice.
Methods:  BALB/cJBomTac mice were immunized intraperitoneally with ovalbumin (OVA) using a low dose sensitization protocol. Throughout the experiment, mice were kept on isocalorical liquid diets containing 0 to 6.2% ethanol. Evaluation of immunomodulatory effects of ethanol was based on measurements of total serum IgE, as well as OVA-specific IgE, IgG1, and IgG2a. Furthermore, levels of OVA-induced interleukin (IL)-4 and interferon- γ were determined in ex vivo splenocyte cultures.
Results:  Alcohol intake decreased the level of OVA-specific IgG2a in a dose-dependent manner, whereas high levels of alcohol markedly increased the level of total IgE, but not OVA-specific IgE. Th1 suppression was supported by the cytokine profile.
Conclusions:  Alcohol consumption induced a marked decrease in markers of the Th1-type allergen-specific immune response and an increase in total serum IgE. In this model, there was no effect of alcohol on OVA-specific IgE. Studies using other routes of immunization may be warranted.     

The enduring influence of drinking motives on alcohol consumption after fateful trauma

Objective: Drinking motives predict later levels of alcohol consumption and development of alcohol dependence, but their effects on stress‐related drinking are less clear. Proximity to the terrorist attack on the World Trade Center (WTC) on 9/11/01 was significantly associated with alcohol consumption 1 and 16 weeks after 9/11/01. We investigated the relationship between drinking motives measured a decade earlier, proximity to the WTC, and drinking after 9/11/01. This event constitutes a natural experiment for studying the effects of previously measured drinking motives on alcohol consumption after fateful trauma. Methods: Adult drinkers (N = 644) residing in a New Jersey county were evaluated for four drinking motives: coping with negative affect, for enjoyment, for social facilitation and social pressure. After 9/11/01, their exposure to the WTC attack and subsequent drinking were assessed. Poisson regression was used to assess the relationships between proximity to the WTC, drinking motives and post‐9/11/01 drinking; models were adjusted for alcohol dependence, age, gender and race. Results: Drinking to cope with negative affect predicted alcohol consumption 1 week after 9/11/01 (p = 0.04) and drinking for enjoyment predicted drinking 1 and 16 weeks after 9/11/01 (p = 0.001 and 0.01, respectively). The associations were independent of proximity to the WTC. No interactions were observed between drinking motives, proximity to the WTC or lifetime alcohol dependence. Conclusion: Drinking motives a decade earlier predicted higher alcohol consumption after fateful trauma independently from proximity to the WTC on 9/11/01. Results suggest that drinking motives constitute a robust, enduring influence on drinking behavior, including after traumatic experiences.     

Effects of stress on alcohol consumption in rats selectively bred for high or low alcohol drinking

BACKGROUND: Stress has long been thought to influence the initiation and maintenance of alcohol drinking in humans. However, results of studies in animals suggest that the relationship between stress and alcohol drinking is not well understood. The purpose of this study was to examine the effect of unpredictable and uncontrollable restraint stress on alcohol consumption in two sets of rat lines selectively bred for alcohol preference (P) and high alcohol drinking (HAD1) and for alcohol nonpreference (NP) and low alcohol drinking (LAD1). METHODS: Male P (n = 26) and NP (n = 26) and HAD1 (n = 17) and LAD1 (n = 20) rats were counterbalanced on the basis of alcohol intake and assigned, in matched pairs, to either a stress (Stress) or a no-stress (Control) group. All rats were given a free choice between a 10% v/v alcohol solution and water, with food freely available. Unpredictable, uncontrollable stress, which consisted of immobilization in a nylon restraint sleeve for 30 to 120 min/day, was applied for 10 consecutive days. RESULTS: Stress moderately reduced alcohol intake in both P and HAD1 rats versus controls and had no effect on alcohol intake in either the NP or the LAD1 rats during the 10 days of stress application. Alcohol intake was increased for the first 5 days after stress termination in P rats but not in HAD1 rats. Alcohol intake remained stable for several weeks in both the NP and LAD1 lines after stress termination and then increased during the last 15 days of the 35-day poststress period in NP rats, but not in LAD1 rats. CONCLUSIONS: A reduction in alcohol intake during stress in rats with a genetic predisposition toward high alcohol intake seems to be a moderate but consistent finding, whereas an increase in alcohol intake after stress termination is less consistent and may be influenced by genetic background.