Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor

Background: Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). Results: We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Conclusions: Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders. © 2009 Society of Biological Psychiatry.

Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption.

AIMS: To investigate the relationship of alcohol consumption with the metabolic syndrome and diabetes in a population-based study with high mean alcohol consumption. Few data exist on these conditions in high-risk drinkers. METHODS: In 6172 adults aged 35-75 years, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and ≥ 35 drinks/week or as non-drinkers (0), low-risk (1-13), medium-to-high-risk (14-34) and very-high-risk (≥ 35) drinkers. Alcohol consumption was objectively confirmed by biochemical tests. In multivariate analysis, we assessed the relationship of alcohol consumption with adjusted prevalence of the metabolic syndrome, diabetes and insulin resistance, determined with the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Seventy-three per cent of participants consumed alcohol, 16% were medium-to-high-risk drinkers and 2% very-high-risk drinkers. In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA-IR decreased with low-risk drinking and increased with high-risk drinking. Adjusted prevalence of the metabolic syndrome was 24% in non-drinkers, 19% in low-risk (P<0.001 vs. non-drinkers), 20% in medium-to-high-risk and 29% in very-high-risk drinkers (P=0.005 vs. low-risk). Adjusted prevalence of diabetes was 6.0% in non-drinkers, 3.6% in low-risk (P<0.001 vs. non-drinkers), 3.8% in medium-to-high-risk and 6.7% in very-high-risk drinkers (P=0.046 vs. low-risk). Adjusted HOMA-IR was 2.47 in non-drinkers, 2.14 in low-risk (P<0.001 vs. non-drinkers), 2.27 in medium-to-high-risk and 2.53 in very-high-risk drinkers (P=0.04 vs. low-risk). These relationships did not differ according to beverage types. CONCLUSIONS: Alcohol has a U-shaped relationship with the metabolic syndrome, diabetes and HOMA-IR, without differences between beverage types.

Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A study of moderating influences of adolescent alcohol drinking conditioned by perception of peer alcohol drinking

Despite a long history of prevention efforts and federal laws prohibiting the consumption of alcohol for those below the age of 21 years, underage drinking continues at both a high prevalence rate and high incidence rate. The purpose of this research study is to explain underage drinking of alcohol conditioned by perception of peer drinking. An acquisition model is conjectured and then a relationship within the model is explained with a national sample of students. From a developmental perspective, drinking alcohol is acquired in a reasonably ordered fashion that reflects the influences over time of the culture, family, and peers. The study measures perceptions of alcohol drinking during early adolescence when alcohol use begins the maintenance phase of the behavior. The correlation between drinking alcohol and perception of classmate drinking can be described via social learning theory. Simultaneously the moderating effects of grade level, gender, and race/ethnicity are used to explain differences between groups. Multilevel logistic regression was used to analyze the relations. The researcher found support for an association between adolescent drinking and perceptions of classmate drinking. Gender and grade level moderated the relation. African-Americans consistently demonstrated less drinking and less perception of classmate drinking than either whites or other students not white nor African-American. The importance of a better understanding of the process of acquiring drinking behaviors is discussed in relation to future research models with longitudinal data. ^

Pregnancy, alcohol intake, and intimate partner violence among men and women attending drinking establishments in a Cape Town, South Africa township.

The highest rates of fetal alcohol syndrome worldwide can be found in South Africa. Particularly in impoverished townships in the Western Cape, pregnant women live in environments where alcohol intake during pregnancy has become normalized and interpersonal violence (IPV) is reported at high rates. For the current study we sought to examine how pregnancy, for both men and women, is related to alcohol use behaviors and IPV. We surveyed 2,120 men and women attending drinking establishments in a township located in the Western Cape of South Africa. Among women 13.3% reported being pregnant, and among men 12.0% reported their partner pregnant. For pregnant women, 61% reported attending the bar that evening to drink alcohol and 26% reported both alcohol use and currently experiencing IPV. Daily or almost daily binge drinking was reported twice as often among pregnant women than non-pregnant women (8.4% vs. 4.2%). Men with pregnant partners reported the highest rates of hitting sex partners, forcing a partner to have sex, and being forced to have sex. High rates of alcohol frequency, consumption, binge drinking, consumption and binge drinking were reported across the entire sample. In general, experiencing and perpetrating IPV were associated with alcohol use among all participants except for men with pregnant partners. Alcohol use among pregnant women attending shebeens is alarmingly high. Moreover, alcohol use appears to be an important factor in understanding the relationship between IPV and pregnancy. Intensive, targeted, and effective interventions for both men and women are urgently needed to address high rates of drinking alcohol among pregnant women who attend drinking establishments.

The complexity of drinking: Interactions between the cognitive and behavioural determinants of alcohol consumption

This study expanded the earlier work conducted by this laboratory ( Hasking, P.A. and Oei, T.P.S. (2002a) . The differential role of alcohol expectancies, drinking refusal self-efficacy and coping resources in predicting alcohol consumption in community and clinical samples. Addiction Research and Theory , 10 , 465-494), by examining the independent and interactive effects of avoidant coping strategies, positive and negative expectancies and self-efficacy, in predicting volume and frequency of alcohol consumption in a sample of community drinkers. Differential relationships were found between the variables when predicting the two consumption measures. Specifically, while self-efficacy, seeking social support for emotional reasons and using drugs or alcohol to cope were independently related to both volume and frequency of drinking, complex interactions with positive and negative alcohol expectancies were also found. These interactions are discussed in terms of the cognitive and behavioural mechanisms thought to underlie drinking behaviour.

A prospective study of personality features predictive of early adolescent alcohol misuse

Personality factors implicated in alcohol misuse have been extensively investigated in adult populations. Fewer studies have clarified the robustness of personality dimensions in predicting early onset alcohol misuse in adolescence. The aim of this study was to examine the predictive utility of two prominent models of personality (Cloninger, 1987; Eysenck & Eysenck, 1975) in emergent alcohol misuse in adolescence. One hundred and 92 secondary school students (mean age = 13.8 years, SD = 0.5) were administered measures of personality (Revised Junior Eysenck Personality Questionnaire – abbreviated; Temperament scale of Junior Temperament and Character Inventory) and drinking behavior (quantity and frequency of consumption, Alcohol Use Disorders Identification Test) at Time 1. At 12-month follow-up, 170 students (88.5%) were retained. Hierarchical multiple regressions revealed the dimensions of psychoticism, extraversion, and Novelty-Seeking to be the most powerful predictors of future alcohol misuse in adolescents. Results provide support for the etiological relevance of these dimensions in the development of early onset alcohol misuse. Findings can be used to develop early intervention programs that target personality risk factors for alcohol misuse in high-risk youth.

Game On: Know Alcohol - Co-creating a tailored alcohol social marketing program

Research demonstrates that education programs are more effective when their target audiences and other key stakeholder groups are involved in the design. The majority of programs continue to be researcher and expert driven. This study extends upon previous research by employing a co-creation research design to offer a consumer driven alternative to education program design. Two co-creation groups involving twenty 14-16 year old Year 10 students who had previously participated in the Game On:Know Alcohol (GOKA) program, which aims to moderate alcohol drinking attitudes and behaviour, were conducted. Analysis revealed that a co-created GOKA program will differ substantially from the researcher and expert driven program that is currently being field tested. Students prefer interactive activities and activities that engage and challenge. Co-creation offers the potential to contest researcher and expert views and may offer to assist in the generation of new insights for the development of education programs.

Game On: Know Alcohol - Interim findings from the first nine schools

A six module program designed to 1) show students the effects of alcohol, 2) impart knowledge of standard drinks and 3) provide students with strategies to moderate (or abstain) from alcohol drinking, is currently being tested in a cluster randomised control design in Queensland. This paper presents immediate evaluation results for the program that was designed using the eight National Social Marketing Centre (2009) benchmark criteria. Students have participated in baseline and/or immediate follow up evaluation in six intervention and three control schools to date. Early results suggest that Game On:Know Alcohol increases knowledge relating to alcohol and moderates attitudes towards binge drinking while maintaining behavioural intentions to drink alcohol excessively. Limitations of the current study and opportunities for future research are outlined.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

School-related predictors of smoking, drinking and drug use: Evidence from the Belfast Youth Development Study

Objective

To examine whether students’ school engagement, relationships with teachers, educational aspirations and involvement in fights at school are associated with various measures of subsequent substance use.
Methods

Data were drawn from the Belfast Youth Development Study (n = 2968). Multivariate logistic models examined associations between school-related factors (age 13/14) and substance use (age 15/16).
Results

The two factors which were consistently and independently associated with regular substance use among both males and females were student–teacher relationships and fighting at school: positive teacher-relationships reduced the risk of daily smoking by 48%, weekly drunkenness by 25%, and weekly cannabis use by 52%; being in a fight increased the risk of daily smoking by 54%, weekly drunkenness by 31%, and weekly cannabis use by 43%. School disengagement increased the likelihood of smoking and cannabis use among females only.
Conclusion

Further research should focus on public health interventions promoting positive relationships and safety at school.