Effect of Paternal Alcohol and Drug Dependence on Offspring Conduct Disorder: Gene-Environment Interplay

Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design.

Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder.

After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history.

Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.


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Request Reprint E-Mail: rhaber@odd.stanford.edu

Racial/Ethnic Differences in Adolescent Substance Use: Mediation by Individual, Family, and School Factors

This study examined racial/ethnic differences in alcohol, cigarette, and marijuana use among a diverse sample of approximately 5,500 seventh and eighth graders. We also evaluated the extent to which individual, family, and school factors mediated racial/ ethnic disparities in use.

Students (49% male) from 16 participating middle schools in southern California reported on lifetime and past-month substance use, individual factors (expectancies and resistance self-efficacy), family factors (familism, parental respect, and adult and older sibling use), and school factors (school-grade use and perceived peer use). We used generalized estimating equations to examine the odds of consumption for each racial/ethnic group adjusting for sex, grade, and family structure. Path analysis models tested mediation of racial/ethnic differences through individual, family, and school factors.

After adjusting for sex, grade, and family structure, Hispanics reported higher and Asians reported lower lifetime and past-month substance use, compared with non-Hispanic Caucasians. Rates of substance use did not differ between non-Hispanic African Americans and Caucasians. Several individual factors mediated the relationship between Hispanic ethnicity and substance use, including negative expectancies and resistance self-efficacy. Higher use among Hispanics was generally not explained by family or school factors. By contrast, several factors mediated the relationship between Asian race and lower alcohol use, including individual, family (parental respect, adult and older sibling use), and school (perceived peer use, school-grade use) factors.


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Request Reprint E-Mail: Regina_Shih@rand.org


Results highlight the importance of targeting specific individual, family, and school factors in tailored intervention efforts to reduce substance use among young minority adolescents.

Course of Alcohol Dependence Among Vietnam Combat Veterans and Nonveteran Controls

Identifying developmental trajectories of alcohol use is fundamental in building theories of alcoholism etiology and course. The purpose of this study was to replicate and generalize our previous finding that had been based on a twin sample drawn from the Vietnam Era Twin Registry. In this study, we made use of a nontwin sample of Vietnam veterans drawn from the Vietnam Era Study--a 25-year follow-up of the Vietnam Drug User Returns project that assessed the long-term medical and psychiatric consequences of substance abuse or dependence in Vietnam.

Alcohol-related behaviors and psychiatric status were assessed in a sample of 839 individuals that comprised 323 veterans who tested positive for drugs (i.e., opiates, barbiturates, or amphetamines) on discharge from Vietnam, 319 veterans who tested negative for drugs at that time, and a nonveteran control sample (n = 197). Individuals with a lifetime diagnosis of alcohol dependence (n = 293) were selected for further analysis. Using detailed life history charts, in-person structured interviews were conducted, which entailed retrospective reports covering the 25 years since the 1972 survey. Measures of alcohol and drug use as well as psychiatric symptoms were obtained by assessing each year of the follow-up interval, beginning with 1972.

Using latent growth mixture modeling, a four-class model was identified with trajectories that were parallel to those identified in our previous studies based on the Vietnam Era Twin Registry: severe chronic alcoholics, severe nonchronic alcoholics, late-onset alcoholics, and young-adult alcoholics.

Present findings provide additional support for the replicability and generalizability of meaningful differences in the course of alcoholism from early adulthood to midlife.

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Request Reprint E-Mail: tjacob@odd.stanford.edu

Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders

Psychological distress (PD) includes symptoms of depression and anxiety and is associated with considerable emotional suffering, social dysfunction and, often, with problematic alcohol use. The rate of current PD among American Indian women is approximately 2.5 times higher than that of U.S. women in general.

Our study aims to fill the current knowledge gap about the prevalence and characteristics of PD and its association with self-reported current drinking problems among American Indian mothers whose children were referred to screening for fetal alcohol spectrum disorders (FASD).

Secondary analysis of cross-sectional data was conducted from maternal interviews of referred American Indian mothers (n=152) and a comparison group of mothers (n=33) from the same Plains culture tribes who participated in an NIAAA-funded epidemiology study of FASD. Referred women were from one of six Plains Indian reservation communities and one urban area who bore children suspected of having an FASD. A 6-item PD scale (PD-6, Cronbach's alpha=.86) was constructed with a summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple statistical tests were used to examine the characteristics of PD and its association with self-reported current drinking problems.

Referred and comparison mothers had an average age of 31.3 years but differed (respectively) on: education, PD-6 mean scores, current prevalence of serious PD, and a current drinking problem. Among referred mothers, those with a current drinking problem had a significantly higher mean PD-6 score. Having PD, serious PD, and 2 specific scale items significantly increased the odds that a referred mother would have a current drinking problem.

Psychological distress among referred mothers is significantly associated with having a self-reported drinking problem. FASD prevention requires multi-level prevention efforts that provide real opportunities for educational attainment and screening and monitoring of PD and alcohol use during the childbearing years. Mixed methods studies are needed to illuminate the social and cultural determinants at the base of the experience of PD and to identify the strengths and protective factors of unaffected peers who reside within the same communities.

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Racial/Ethnic Differences in Adolescent Substance Use: Mediation by Individual, Family, and School Factors

This study examined racial/ethnic differences in alcohol, cigarette, and marijuana use among a diverse sample of approximately 5,500 seventh and eighth graders. We also evaluated the extent to which individual, family, and school factors mediated racial/ ethnic disparities in use.

Students (49% male) from 16 participating middle schools in southern California reported on lifetime and past-month substance use, individual factors (expectancies and resistance self-efficacy), family factors (familism, parental respect, and adult and older sibling use), and school factors (school-grade use and perceived peer use).

We used generalized estimating equations to examine the odds of consumption for each racial/ethnic group adjusting for sex, grade, and family structure. Path analysis models tested mediation of racial/ethnic differences through individual, family, and school factors.

After adjusting for sex, grade, and family structure, Hispanics reported higher and Asians reported lower lifetime and past-month substance use, compared with non-Hispanic Caucasians.

Rates of substance use did not differ between non-Hispanic African Americans and Caucasians.

Several individual factors mediated the relationship between Hispanic ethnicity and substance use, including negative expectancies and resistance self-efficacy.

Higher use among Hispanics was generally not explained by family or school factors.

By contrast, several factors mediated the relationship between Asian race and lower alcohol use, including individual, family (parental respect, adult and older sibling use), and school (perceived peer use, school-grade use) factors.

Results highlight the importance of targeting specific individual, family, and school factors in tailored intervention efforts to reduce substance use among young minority adolescents.


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Distribution of ADH1B, ALDH2, CYP2E16, and CYP2E17B genotypes in Turkish population

The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH).

The genetic variation of ADH1B, ALDH2, and CYP2E1
is different among racial populations and cause difference in elimination rates of alcohol.

The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations.

ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method.

ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population.

The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon.

For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected.

According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations.

This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence.

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Request Reprint E-Mail: kayaalti@medicine.ankara.edu.tr

Alcohol dependence and glutamate decarboxylase gene polymorphisms in an Italian male population

Knowledge of alcohol use disorder and of substance-related problems has recently found some initial support in genetic studies.

With a view to further understanding of this particular aspect, in the light of the “self-medication hypothesis,” we focused our attention on the gamma aminobutyric acid system and, in particular, on single nucleotide polymorphisms (SNPs) in the glutamate decarboxylase 67 or glutamic acid decarboxylase 67 (GAD67) gene region in association with alcohol dependence.

The research was structured as a case–control study. The patient cohort included 283 Caucasian males from the Veneto region, North-east Italy; 107 were alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV TR) criteria, and 176 were controls recruited from blood donors.

We analyzed 26 SNPs located in the coding and untranslated regions of the GAD67 gene with the GenomeLab SNPStream Genotyping System (Beckman Coulter, Fullerton, CA). Fisher's Chi-square test for allele and genotype distributions and Hardy–Weinberg equilibrium analysis for cases and controls were performed. Ten SNPs at the GAD67 gene were valid for further statistics.

Preliminary results show a difference in genotype distribution (P=.003; χ2=11.6081) between alcoholic subjects and controls of SNP rs 11542313 located in exon 3 of the GAD67 gene, responsible for a silent mutation (His37His).

This is the first genetic study regarding the GAD67 gene in relation to the condition of alcohol dependence in an Italian population of subjects all coming from the same region (Veneto). The results highlight a statistical association between one SNP of GAD67 and the condition of alcohol dependence.

To clarify the possible meaning of this association, further genetic analyses are being undertaken. In particular, we are investigating other genetic polymorphisms, both upstream and downstream from rs 11542313, which may interfere with splicing and/or GAD67 mRNA stability.



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Request Reprint E-Mail: claudio.terranova@sanita.padova.it

Contributions of Studies on Alcohol Use Disorders to Understanding Cerebellar Function

Neuropathological, neuropsychological, and neuroimaging studies of human alcoholism provide evidence for degradation of frontal, pontine, thalamic, and cerebellar brain sites and disturbed associated functions.

Current studies using neuroimaging combined with examination of executive functions, traditionally considered the sole purview of the frontal lobes, have identified a role for the cerebellum serving as a compensatory processing adjunct to enable normal performance on challenging tasks tapping executive functions.

This overview proposes that disruption of an executive frontocerebellar network is a major contributor to characteristic behaviors of alcoholism that, on the one hand, enable alcohol use disorders, and on the other hand, lead to compensation for dysfunctions in alcoholism traditionally considered frontally-based.


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Request Reprint E-Mail: nzahr@stanford.edu

The Co-occurrence of Alcohol Abuse in Alcohol Dependence Among a Treatment Sample of Asian/Pacific Islanders

Alcohol abuse is not always linked to alcohol dependence in the general population, especially among minorities and women. These studies have excluded Asian and Pacific Islanders from analyses.

We examine the prevalence of alcohol dependence with and without alcohol abuse among a treatment sample in Hawaii.

Two hundred twenty-five participants were recruited from 2 major residential treatment programs in Hawaii for an 89% response rate. Participants were interviewed as soon as possible after their admission, generally within the first week. Abuse and dependence criteria were assessed with the Diagnostic Interview Schedule.

One hundred and eighteen (52%) met criteria for alcohol dependence. Among respondents with current alcohol dependence, 17% did not additionally meet criteria for abuse among clients at facilities in Hawaii. Current dependence without abuse occurred more frequently among Native Hawaiian clients (20%) and less frequently among Asian clients (11%). Although the number of women in the study was small, current dependence without abuse occurred more frequently among women (25%) compared with men (14%).

This study contributes to the current state of knowledge with regards to co-occurrence of alcohol abuse and dependence among ethnic groups in Hawaii. It will help treatment facilities develop a better understanding of the individuals seeking treatment in an effort to develop a comprehensive treatment plan that will take into account ethnic considerations. In addition, the use of alcohol abuse as a screening method for alcohol dependence in epidemiologic studies may underestimate the prevalence of dependence among Pacific Islanders, further limiting access to services for this underserved group.

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Request Reprint E-Mail: goebertd@dop.hawaii.edu

Collegiate natural drinking groups: Characteristics, structure, and processes

College students typically consume alcohol in groups.

To examine group characteristics, structure, processes, and group drinking, we conducted semi-structured, in-depth interviews with 30 (50% female; 60% non-Latino White) college students (18–24 years old).

Participants described the last event they attended where alcohol was present.

The interviews were fully transcribed and coded using an inductive approach with the software ATLAS.ti 5.2.

The findings revealed that group formation often involved minimal planning and was facilitated by technologies such as phone, text messaging, and social networking Internet sites.

Multiple roles were identified that supported the groups and that pertained to the drinking event organization, to drinking activities, or group regulation.

As the groups reached drunkenness, decision negotiations were replaced by random actions that often exemplified the loss of judgment resulting from alcohol impairment, leading to risky situations.

Understanding group dynamics and social roles in drinking groups could inform prevention efforts by identifying new loci of interventions; promoting pro-social roles in the group could encourage peers to become effective agents of prevention within the group.


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Request Reprint E-Mail: jlange@mail.sdsu.edu

What do clients want from alcohol and other drug treatment services? A mixed methods examination

This article presents findings from a study that examined the assistance aspirations of clients attending an outpatient alcohol and other drug (AOD) treatment service.

Key research questions were as follows: What type(s) of assistance do clients want? Do assistance aspirations vary by age, gender or ethnicity? and Are assistance aspirations predictive of subsequent attendance duration?

The study was set in an outpatient AOD treatment service located in Auckland, New Zealand. Data were collected from two client groups via a questionnaire (n = 109) and a semi-structured interview (n = 12). Questionnaire data were collected following the completion of the first attended appointment. Interview data were completed, on average, after participants had attended two treatment appointments (range 1–3).

When asked to indicate the services they would most like to receive, from a list of 10 possible options, questionnaire participants most frequently selected the options ‘talk to a professional about an AOD-related problem’ (71%), ‘practical strategies for making/maintaining changes to AOD use’ (66%) and ‘ongoing support while making/maintaining changes to AOD use’ (61%).

These options were also the three most likely to be endorsed as the number one service type wanted. Binary regression analysis identified few between-group differences concerning the frequency with which each option was endorsed.

The interview data were consistent with the questionnaire findings suggesting that, irrespective of age, gender, ethnicity and subsequent attendance duration, outpatient AOD treatment clients may share a common set of assistance aspirations at the point of service entry.


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Request Reprint E-Mail: justin.pulford@pngimr.org.pg

Interventions delivered during antenatal care to reduce alcohol consumption during pregnancy: A systematic review

Despite the importance of reducing prenatal exposure to alcohol, a recent Cochrane review found limited evidence from randomised controlled trials (RCTs) regarding effectiveness of interventions to reduce drinking during pregnancy.

The aim of this systematic review was to consider additional evidence by including RCTs and non-RCTs to determine whether pregnant women reduced alcohol consumption during pregnancy following interventions delivered during antenatal care.

Five electronic databases were searched using keywords: e.g. pregnancy, maternal, alcohol, consumption, drinking, cognitive-behavioural therapy, motivational interviewing (MI), brief intervention, health education, social support and self-efficacy.

Papers were excluded through a consecutive method using the title, abstract and full text paper. Two authors assessed the full text papers, including quality assessment.

Eight trials were included in the review, including six RCTs and two non-RCTs. Interventions included brief interventions, MI, a self-help manual, supportive counselling, high feedback ultrasound and basic educational interventions.

In general, methodological quality in all but two studies was poor, limiting the conclusions that could be drawn from this review.

However, there was some evidence from a small number of studies that single-session face-to-face brief interventions resulted in positive effects on the maintenance of alcohol abstinence during pregnancy.

Women choosing abstinence as their drinking goals and heavier drinking women who participated with a partner were more likely to be abstinent at follow-up.

However, more intensive interventions may be required to encourage women who continue to drink during pregnancy to reduce their consumption.

Implications for practice and future research directions are discussed.


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Request Reprint E-Mail: a.s.gilinsky@stir.ac.uk

Do Psychological Variables Mediate Sex Differences in Young Adults’ Alcohol Use?

This study applied an extended theory of planned behavior to test whether psychological variables mediate sex differences in alcohol consumption in social contexts.

Questionnaires of 300 young adults (urban, mean age 25 years, 49% female) were collected in 2007 prior to a sociable drinking occasion; consumption data were obtained through telephone interviews thereafter. The multiple-path mediation model was analyzed using structural equation modeling.

Sex differences in alcohol consumption, which were considerable, were partly mediated by the significant specific indirect effects of subjective norms through intention and of self-efficacy through both intention and willingness. Body weight was not a significant mediator.

Limitations are noted and implications for future research are discussed.


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Request Reprint E-Mail: friederike.zimmermann@psychologie.uni-heidelberg.de

Alcohol News 36/2010

BBC News (Scotland) - Alcohol price pilot claims 'damage' Scottish Borders
An MSP has criticised a south of Scotland colleague who suggested the Borders should pilot plans for a minimum price per unit of alcohol.
http://www.bbc.co.uk/news/uk-scotland-south-scotland-11199418

Telegraph.co.uk (UK) - Academic stress 'pushing young girls to alcohol and cigarettes'
Academic stress and the pressure to look attractive are driving young girls to alcohol and cigarettes, according to a study by the Girl Guides.
http://www.telegraph.co.uk/news/uknews/7982648/Academic-stress-pushing-young-girls-to-alcohol-and-cigarettes.html

Herald Scotland (Scotland) - Minimum pricing will help reduce the human cost of alcohol abuse
The opposition parties are acting irresponsibly over the Scottish Government’s proposals to introduce a minimum alcohol price of 45p per unit (“Sturgeon sets the minimum price of alcohol at 45p a unit”, The Herald, September 3).
http://www.heraldscotland.com/comment/herald-letters/letters-monday-6-september-2010-1.1053036

USA Today - 3 to 4 drinks per week may raise risk of breast cancer's return
Drinking even moderate amounts of alcohol may raise the risk for breast cancer recurrence in some women, new research indicates.
http://www.usatoday.com/yourlife/health/medical/breastcancer/2010-09-06-alcohol-drinking_N.htm

Sunday Business Post (Ireland) - Government advised to ban alcohol firms from sponsoring sporting events
Proposals to ban sponsorship of sports and other events by drinks companies are expected to be included in a report to government to be finalised next month, writes Pat Leahy.
http://www.sbpost.ie/news/government-advised-to-ban-alcohol-firms-from-sponsoring-sporting-events-51509.html

TestCountry.com - Fetal Brain Size Affected by Alcohol Consumption
Mothers who continue to drink even at an early stage of pregnancy do not only endanger themselves but their babies as well.
http://hometestingblog.testcountry.com/?p=9581

FLEXNEWS (Kenya) - Kenyan Market Frets Over Impact of New Alcohol Law
A new Kenyan alcohol law could open up East African Breweries to competition, with micro-brewers springing up to capitalise on the legalisation of traditional liquors, analysts said.
http://www.flex-news-food.com/console/PageViewer.aspx?page=32024

Helsinki Times (Finland) - Doctors to order alcohol locks for risk patients
A law enabling Finnish doctors to recommend alcohol locks on the cars of patients who consume a lot of alcohol is to come into use soon, according to regional daily Aamulehti on Monday.
http://www.helsinkitimes.fi/htimes/domestic-news/general/12374-doctors-to-order-alcohol-locks-for-risk-patients-aamulehti-.html

AFP (Russia) - Russians urged to smoke, drink more
Smoke and drink more, Russia's finance minister Alexei Kudrin urged citizens on Wednesday, explaining that higher consumption would help lift tax revenues for spending on social services.
http://www.google.com/hostednews/afp/article/ALeqM5jGzvnPQDSDAZ-_szkxN65OwffAKA

DailyFinance (USA) - Alcohol and College: How Much Money Are Students Really Drinking?
The average college student spends $500 per year on alcohol, according to Rachel Barrington of the University of Wisconsin.
http://www.dailyfinance.com/story/alcohol-college-money-cost-students-drinking/19620570/

NewsOK.com (USA) - Millions drive drunk, government study finds
An estimated 17 million people have driven while drunk at least once on U.S. streets and highways in the course of a year, according to a government study released last week.
http://newsok.com/millions-drive-drunk-government-study-finds/article/3491952

NDTV.com - Judging when alcohol's effects wear off not easy
The way that alcohol impairs reasoning and problem-solving abilities may explain why some people feel they are fit to drive even though they are drunk.
http://doctor.ndtv.com/storypage/ndtv/id/4711/Judging_when_alcohols_effects_wear_off_not_easy.html

MedIndia (Sweden) - Privatizing Retail Alcohol Sales in Sweden Will Escalate Alcohol-Related Violence
Privatizing Sweden's government monopoly on the sale of alcohol, a study published today in the scientific journal Addiction argues, will significantly increase alcohol-related violence and other harms.
http://www.medindia.net/news/Privatizing-Retail-Alcohol-Sales-in-Sweden-Will-Escalate-Alcohol-Related-Violence-73538-1.htm

YLE News (Finland) - Psychiatrists Propose Forcing Sobriety on Violent Criminals
Finland's leading forensic psychiatrists are calling for violent convicts to prove their sobriety as a condition for freedom. According to the proposal, prisoners who are considered dangerous should not be released unless they have committed to sobriety.
http://www.yle.fi/uutiset/news/2010/09/psychiatrists_propose_forcing_sobriety_on_violent_criminals_1951377.html

WHO (Africa) - WHO proposes strategy to reduce harmful use of alcohol
The World Health Organization has proposed a strategy to prevent or at least reduce the harmful use of alcohol and related problems in the African Region.
http://www.afro.who.int/en/media-centre/pressreleases/2402-who-proposes-strategy-to-reduce-harmful-use-of-alcohol.html


Alcohol News

Accumbens Homer2-mediated signaling: A factor contributing to mouse strain differences in alcohol drinking?

Alcohol-induced increases in nucleus accumbens glutamate actively regulate alcohol consumption and the alcohol responsiveness of corticoaccumbens glutamate systems relates to genetic variance in alcohol reward.

Here, we extend earlier data for inbred mouse strain differences in accumbens glutamate by examining for differences in basal and alcohol-induced changes in the striatal expression of glutamate-related signaling molecules between inbred C57BL/6J and DBA2/J mice.
Repeated alcohol treatment (8 X 2 g/kg) increased the expression of Group1 metabotropic glutamate receptors, the NR2a/b subunits of the N-methyl-D-aspartate receptor, Homer2a/b, as well as the activated forms of protein kinase C epsilon and phosphoinositol-3-kinase within ventral, but not dorsal, striatum.

Regardless of prior alcohol experience, C57BL/6J mice exhibited higher accumbens levels of mGluR1/5, Homer2a/b, NR2a and activated kinases versus DBA2/J mice, while an alcohol-induced rise in dorsal striatum mGluR1/5 expression was observed only in C57BL/6J mice.

We next employed virus-mediated gene transfer approaches to ascertain the functional relevance of the observed strain difference in accumbens Homer2 expression for B6/D2 differences in alcohol-induced glutamate sensitization, as well as alcohol preference/intake.

Manipulating NAC shell Homer2b expression actively regulated these measures in C57BL/6J mice, while DBA2/J mice were relatively insensitive to the neurochemical and behavioral effects of virus-mediated changes in Homer2 expression.

These data support the over-arching hypothesis that augmented accumbens Homer2-mediated glutamate signaling may be an endophenotype related to genetic variance in alcohol consumption.

If relevant to humans, such data pose polymorphisms affecting glutamate receptor/Homer2 signaling in the etiology of alcoholism.

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Request Reprint E-Mail: szumlinski@psych.ucsb.edu

A Review of Synaptic Plasticity at Purkinje Neurons with a Focus on Ethanol-Induced Cerebellar Dysfunction

The cerebellum controls balance, posture, motor coordination, and cognition, and studies suggest that ethanol impairs these cerebellar functions. However, the mechanisms through which ethanol produces these effects are not fully understood.

Here, we review evidence suggesting that ethanol acts, in part, by impairing synaptic plasticity mechanisms at cerebellar Purkinje neurons.

We will primarily focus on recent experiments indicating that long-term depression at both parallel fiber– and climbing fiber–Purkinje cell synapses is inhibited by acute ethanol exposure.

We will also discuss experimental evidence showing that chronic prenatal ethanol exposure converts long-term depression into long-term potentiation at parallel fiber–Purkinje cell synapses.


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Request Reprint E-Mail: fvalenzuela@salud.unm.edu

Bk Channel and Alcohol, a Complicated Affair

Alcohol is a fast acting molecule that alters behavior within a few minutes of absorption. Its rapid behavioral impact suggests early action on ion channels.

Of all voltage-gated potassium ion channels, BK channels, a subcategory of potassium channels characterized by their large unitary conductance, and by their capacity of being activated synergistically by membrane potential and intracellular free calcium, are unique due to their high sensitivity to alcohol.

In this review, we discuss BK channels structure and function, and how they help us understand the various ways BK channel mediates alcohol's effects on neuronal function and on behavior in the striatum.

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Request Reprint E-Mail: gilles.martin@umassmed.edu

Alcohol and the Prefrontal Cortex

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex.

In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region.

This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol.

The chapter concludes with a discussion of unanswered questions and areas needing further investigation.

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Request Reprint E-Mail: woodward@musc.edu

Ethanol Action on Dopaminergic Neurons in the Ventral Tegmental Area: Interaction with Intrinsic Ion Channels and Neurotransmitter Inputs

The dopaminergic system originating in the midbrain ventral tegmental area (VTA) has been extensively studied over the past decades as a critical neural substrate involved in the development of alcoholism and addiction to other drugs of abuse.

Accumulating evidence indicates that ethanol modulates the functional output of this system by directly affecting the firing activity of VTA dopamine neurons, whereas withdrawal from chronic ethanol exposure leads to a reduction in the functional output of these neurons.

This chapter will provide an update on the mechanistic investigations of the acute ethanol action on dopamine neuron activity and the neuroadaptations/plasticities in the VTA produced by previous ethanol experience.

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Request Reprint E-Mail: morikawa@mail.utexas.edu

Glutamate Plasticity in the Drunken Amygdala: The Making of an Anxious Synapse

Plasticity at glutamatergic synapses is believed to be the cellular correlate of learning and memory. Classic fear conditioning, for example, is dependent upon NMDA-type glutamate receptor activation in the lateral/basolateral amygdala followed by increased synaptic expression of AMPA-type glutamate receptors.

This review provides an extensive comparison between the initiation and expression of glutamatergic plasticity during learning/memory and glutamatergic alterations associated with chronic ethanol exposure and withdrawal.

The parallels between these neuro-adaptive processes suggest that long-term ethanol exposure might “chemically condition” amygdala-dependent fear/anxiety via the increased function of pre- and post-synaptic glutamate signaling.

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Request Reprint E-Mail: bmccool@wfubmc.edu