A grandparent-influenced locus for alcohol preference on mouse chromosome 2

Pharmacogenetics and Genomics: 12 August 2009

Loci on mouse chromosome 2 have previously been associated with ethanol consumption.

Using a limited access choice paradigm, we found that mouse chromosome 2 carries an allelic variant of a locus for ethanol intake and a distinct locus selective for ethanol preference. The heritability of alcoholism has been suggested to be parent-specific, perhaps resulting from genetic imprinting.

Our findings suggest that grandparent-influenced vulnerability for ethanol consumption is conferred by genes on chromosome 2, providing important new leads to enhance our understanding of the heritability of alcoholism.

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Request Reprint E-Mail: mailto:H.M.B.Lesscher@umcutrecht.nl

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Substance Abuse Treatment Facility Locator

This searchable directory of drug and alcohol treatment programs shows the location of facilities around the country that treat alcoholism, alcohol abuse and drug abuse problems.

The Locator includes more than 11,000 addiction treatment programs, including residential treatment centers, outpatient treatment programs, and hospital inpatient programs for drug addiction and alcoholism. Listings include treatment programs for marijuana, cocaine, and heroin addiction, as well as drug and alcohol treatment programs for adolescents, and adults.

CLICK HERE

to enter the drug abuse and alcoholism Treatment Facility Locator

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Managing problem drinking of alcohol – screening and brief intervention

Ceylon Medical Journal Vol. 54, No. 2, June 2009 pp 59-62

It is important to identify and manage problem drinking as it causes a significant burden of disease. There are simple screening procedures and management techniques which are effective in outpatient settings. All doctors should educate themselves and master these skills.

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Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking

Neuropsychopharmacology (2009) 34, 2218–2226

Tobacco smoking is highly comorbid with heavy alcohol drinking, yet the interaction of tobacco smoking and alcohol drinking on brain catecholaminergic synaptic markers is unexplored. Here we evaluate the effects of alcohol drinking alone from comorbid alcohol drinking and tobacco smoking on dopamine (DA) and serotonin (5-HT) transporter availability.

During the first week of abstinence, DA and 5-HT transporter availability is higher in alcohol drinking nonsmokers but not in alcohol drinking smokers.

Smoking appears to suppress neuroadaptive changes in DA and 5-HT transporters during acute withdrawal from alcohol.

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Request Reprint E-Mail: kelly.cosgrove@yale.edu

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Use (and Misuse) of the Responsible Drinking Message in Public Health and Alcohol Advertising: A Review

Health Education & Behavior First Published 10 August 2009

The objective is to present a comparative analysis examining the alcohol industry’s and scholarly researchers’ use of the concept "responsible drinking."

Misunderstanding stemming from the inconsistency and counterintuitive nature of brewer-sponsored "responsible drinking" campaigns is further compounded by researchers’ use of the term and concept of "responsible drinking" in their scholarly reports. In articulating the definition of "responsible drinking," researchers employ subjective notions and personal ideas, thus not differentiating the construct’s meaning from the one acquired in brewer-sponsored campaigns. Researchers are consistently inconsistent when identifying specific health measures that promote and/or contradict responsible alcohol consumption.

To evade the subjective notions of researchers and restrictive impressions attached by the alcohol industry, the manner in which individuals interpret, perceive, and practice responsible drinking must be systematically explored and examined using theoretically based constructs.

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Request Reprint E-Mail: aebarry@purdue.edu

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Blockade of ethanol reward by the kappa opioid receptor agonist U50,488H

Alcohol Volume 43, Issue 5, August 2009, Pages 359-365

Alcoholism is a pervasive social problem, and thus understanding factors that regulate alcohol (ethanol) reward is important for designing effective therapies. One putative regulatory system includes the kappa opioid receptor (KOR) and its endogenous ligand, dynorphin.

Previously, we demonstrated that acute ethanol increased preprodynorphin expression via brain-derived neurotrophic factor (BDNF) in striatal neurons, and that blockade of the KOR attenuated decreases in ethanol intake observed following increased expression of BDNF. As high doses of KOR agonists can generate an aversive state, we hypothesized that endogenous dynorphin may regulate ethanol intake by interfering with the rewarding properties of ethanol.

We found that low, nonaversive doses of the KOR agonist U50,488H blocked the rewarding properties of ethanol during conditioning, thus impairing the acquisition of conditioned place preference. Importantly, we demonstrate that U50,488H also inhibited the conditioned increase in locomotor activation normally observed in the ethanol-paired chamber on test day.

Taken together, these data indicate that the KOR/dynorphin system may acutely regulate ethanol intake via inhibition of the rewarding properties of ethanol.

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Request Reprint E-Mail: dorit.ron@ucsf.edu

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Altering the Relative Abundance of GABAA Receptor Subunits Changes GABA- and Ethanol-Responses in Xenopus Oocytes

Alcoholism: Clinical and Experimental Research Volume 33 Issue 6, Pages 1089 - 1096

Variations in GABRA2 and GABRG3, genes encoding the α2 and γ3 subunits of the pentameric GABAA receptor, are associated with the risk of developing alcoholism in adults, conduct disorder at younger ages, and with differences in electroencephalographic power in the β frequency range. The SNPs associated with alcoholism did not alter the coding of these genes, and extensive DNA sequencing of GABRA2 did not find coding changes in the high-risk haplotypes. Therefore, we hypothesize that the associations arise from differences in gene expression.

These studies demonstrate that changes in relative expression of GABAA receptor subunits alter the response of the resulting channels to GABA and to ethanol.

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Request Reprint E-Mail: johurley@iupui.edu

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Molecular Dissection of a Major Gene Effect on a Quantitative Trait: The Level of Alcohol Dehydrogenase Expression in Drosophila melanogaster

Genetics 144 1559-1564 (December, 1996)

A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melunogaster, is due to multiple polymorphisms within the Adh gene.

These polymorphisms are located in an intron, the coding sequence, and the 3‘ untranslated region. Because of nonrandom associations among polymorphisms at different sites, the individual effects combine (in some cases epistatically) to produce “superalleles” with large effect.

These results have implications for the interpretation of major gene effects detected by quantitative trait locus mapping methods. They show that large effects due to a single locus may be due to multiple associated polymorphisms (or sequential fixations in isolated populations) rather than individual mutations of large effect.

[This classic paper uses P‑element transformation to show that three separate molecular polymorphisms in alcohol dehydrogenase affect the level of gene expression, that these polymorphisms interact epistatically and that the polymorphisms have opposite effects on expression.]

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Prevalence and socio-demographic correlates of substance use in a rural community in Sikkim, North East India: Results from a pilot population survey

Journal of Substance Use First Published 11 August 2009

Sikkim, a province in North East India, inhabited by indigenous population of Lepchas, Bhutias, and Nepalis, lies in the foothills of the Himalayas sharing borders with Tibet, Nepal, and Bhutan. Information on epidemiology of substance use in Sikkim is not available.

Prevalence of substance use has been 76.7% (only alcohol 55.3%, cannabis 13.6%, opioid 5.8%). Most drug users belonged to 15-44 years age group with 74.6% having onset in the 15-20 years age range, but only 3.9% had a history of migration. Knowledge about AIDS was significantly low at 36.7% compared with the non-drug using population (62.5%).

Alcohol use is higher than national prevalence rates requiring targeted intervention.

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Request Reprint E-Mail: amitchakrabarti@hotmail.com

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Front, side, and back-loading: Patrons' rationales for consuming alcohol purchased off-premises before, during, or after attending nightclubs

Journal of Substance Use First Published 11 August 2009

To examine motivations for consumption of alcohol purchased off-trade when visiting on-trade licensed premises.

The findings of this research imply that off-premises alcohol consumption by night-clubbers is widespread and motivated as much by the structure of the night-time economy as by price differentials between competing sectors of the licensed trade.

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Request Reprint E-Mail: Alasdair.Forsyth@gcal.ac.uk

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Gender differences in the choreography of alcohol-related violence: An observational study of aggression within licensed premises

Journal of Substance Use First Published 11 August 2009

To examine patterns of gender involvement in violent incidents observed within licensed premises.

This research the challenges belief that female conflicts within licensed premises are less problematic than those involving males. These findings are discussed in terms of alcohol, masculinity, and harm reduction.

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Request Reprint E-Mail: Alasdair.Forsyth@gcal.ac.uk

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Saints not sinners? Young people bucking the trend of binge drinking. An analysis of the drinking trends of school age children in Sunderland

Drugs: education, prevention and policy First Published 11 August 2009

The main aim of this article was to determine the self-reported drinking behaviours of school age children in Sunderland in the North East of England. The results presented are derived from data collected by a Health Related Behaviour Survey, which was administered by the Schools Health Education Unit (SHEU) of the University of Exeter.

A variety of health and social issues related to alcohol consumption, parental knowledge and protection and the illegal purchasing of alcohol were identified. The survey in Sunderland found little evidence to corroborate previous findings of increased alcohol consumption and indeed binge drinking.

The inferences drawn from the analysis raise some interesting questions relating to the provision of services and long-term health needs of young people.

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Request Reprint E-Mail: A.McInnes@tees.ac.uk

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The Neighborhood Alcohol Environment and Alcohol-Related Morbidity

Alcohol and Alcoholism Advance Access published online on August 10, 2009

The aims of this study were (1) to examine the association between neighborhood alcohol outlet density and individual self-reported alcohol-related health outcomes in the last year—sexually transmitted infections (STI), motor vehicle accidents, injury, liver problems, hypertension and experienced violence; (2) to determine whether the relationship between morbidity and alcohol outlet density is mediated by individual alcohol consumption; and (3) to explore the role of alcohol outlet density in explaining any observed racial and ethnic differences in morbidity.

Findings support the concept that off-premise alcohol outlets in the neighborhood environment may impact health and social outcomes, either directly or indirectly, through individual alcohol consumption and these associations may be heterogeneous with respect to race and ethnicity.

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Request Reprint E-Mail: kthea1@lsuhsc.edu

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Brewers Criticize Excise Tax Initiative

12 August 2009 By Alex Anishyuk / Special to The Moscow Times

A government initiative to triple the excise tax on beer would be disastrous for the brewing industry, resulting in job losses and crippling smaller producers, members of the Beer Producers Union said at a news conference Tuesday.

“The plan being considered by the government will cause production to drop by 40 to 50 percent, and thousands of people will lose their jobs,” said Daniil Briman, vice president of Baltika, the country’s largest brewer. “I don’t think anyone in the government seriously considered the social consequences of this initiative.” . . . . .

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Social Marketing Podcast

An overview of alcohol social marketing for England, Nick Tancock - Social Marketing Advisor to the DH drugs and alcohol team. 2009

Podcast
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PAT (2009)-Revisions to the Paddington Alcohol Test for Early Identification of Alcohol Misuse and Brief Advice to Reduce Emergency Department Re-attendance

The Paddington Alcohol Test (PAT) has evolved over 15 years as a clinical tool to facilitate emergency physicians and nurses giving brief advice and the offer of an appointment for brief intervention by an alcohol nurse specialist. Previous work has shown that unscheduled emergency department re-attendance is reduced by 'making the connection' between alcohol misuse and resultant problems necessitating emergency care. The revised 'PAT (2009)' now includes education on clinical signs of alcohol misuse and advice on when to request a blood alcohol concentration.

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Press Release - Alarming rise in oral cancer rates among forty-somethings

Rates of oral cancers, such as cancers of the mouth, tongue and lip, have increased by around a quarter in the past decade among people in their 40s, according to figures from Cancer Research UK today.

Oral cancer is largely a preventable disease with tobacco and alcohol use being the main risk factors.

Cancers caused by smoking often take up to 30 years to develop, so tobacco is less ikely to be the main reason behind the increase in oral cancer in people in their 40s compared ith older people.

And since smoking rates have gone down and alcohol consumption has gone up, experts believe the increase in oral cancer rates could mainly be down to drinking. . . . . .

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Effective dissemination: An examination of theories and models of change for research dissemination in the AOD field.

In this part (Part Three), the theories and models of change underpinning the use of dissemination strategies and the implications for the alcohol and other drugs (AOD) field are examined. This report provides a summary of key theories and models that have been used in the development of dissemination strategies for facilitating uptake of innovations into practice, or to interpret the outcomes of an evaluation of such strategies.

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Effective dissemination: An examination of the costs of implementation strategies for the AOD field.

This document is Part Two of a 3-part series by the National Centre for Education and Training on Addiction (NCETA) examining the effectiveness, costs and theories related to dissemination and implementation of research into practice. Part One is a systematic literature review that evaluated the effectiveness of 16 different dissemination strategies for facilitating the implementation of new research, programs and treatments to improve outcomes for clients with alcoholand other drug-related problems. Part Two involves an examination of the costs associated with using such strategies, and Part Three is an examination of the theories and models of change underlying the use of strategies.

In this Part, the costs of implementing innovations and the implications of using dissemination strategies for the alcohol and other drug (AOD) field are examined. Part One in this series is a ystematic review of the effectiveness of dissemination and implementation strategies (Bywood, unnay, & Roche, 2008). However, evidence related to economic considerations was not based n a systematic search using relevant terms associated with economic analysis. Rather, it is a summary of the evidence from the systematic review on effectiveness that also contained data on costs of using an implementation strategy.

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Effective dissemination: A systemati review of implementation strategies for the AOD field.

The National Centre for Education and Training on Addiction (NCETA) undertook a systematic literature review of the most commonly used strategies designed to increase the uptake of innovations into professional practice. Analyses were undertaken to evaluate their effectiveness and to determine their relevance and applicability for use in the alcohol and other drugs (AOD) field. By evaluating and synthesising the evidence from a wide range of sources, NCETA aimed to identify the key factors underlying successful dissemination strategies and develop a framework for dissemination and implementation of innovations in the AOD field.

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Interoceptive Effects of Alcohol Require mGlu5 Receptor Activity in the Nucleus Accumbens

The Journal of Neuroscience, July 29, 2009, 29(30):9582-9591

The interoceptive effects of alcohol are major determinants of addiction liability. Metabotropic glutamate (mGlu) receptors are widely expressed in striatal circuits known to modulate drug-seeking.

Given that the interoceptive effects of drugs can be important determinants of abuse liability, we hypothesized that striatal mGlu receptors modulate the interoceptive effects of alcohol.

These results show that mGlu5 receptor activity in the nucleus accumbens is required for the expression of the interoceptive effects of alcohol.

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Request Reprint E-Mail: jbesheer@med.unc.edu

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Ethanol Affects Transforming Growth Factor β1-Initiated Signals: Cross-Talking Pathways in the Developing Rat Cerebral Wall

The Journal of Neuroscience, July 29, 2009, 29(30):9521-9533

TGFβ1 regulates early cortical development by moving young neurons from the proliferative population and promoting their migration. Altered TGFβ1-regulated signaling can lead to abnormal development underlying microencephaly and migratory defects as in attention deficit hyperactivity disorder, dyslexia, and fetal alcohol spectrum disorder.

The present study tested the hypotheses that TGFβ1 signals through cross-talking Smad2/3 and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways and that ethanol simulates these TGFβ1-initiated signals.

In summary, TGFβ1 activates two separate pathways (Smad2/3 and ERK1/2) that actively interact. Ethanol simulates TGFβ1-induced changes in these signaling systems. Each pathway is preferentially activated during specific developmental events: the Smad2/3 pathway is key for cells exiting from the cycling population and the ERK1/2 pathway is particularly inducible during neuronal migration.

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Request Reprint E-Mail: millermw@upstate.edu

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Prosocial Effects of Nicotine and Ethanol in Adolescent Rats Through Partially Dissociable Neurobehavioral Mechanisms

Neuropsychopharmacology advance online publication 5 August 2009

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats.

Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol.

We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at doses that reduced anxiety. The effects of nicotine on social play were blocked by the opioid receptor antagonist naloxone, the CB1 cannabinoid receptor antagonist SR141716A, and the dopamine receptor antagonist -flupenthixol. The effects of ethanol were blocked by SR141716A and -flupenthixol, but not by naloxone. Combined administration of subeffective doses of nicotine and ethanol only modestly enhanced social play.

These results show that the facilitatory effects of nicotine and ethanol on social play are behaviorally specific and mediated through neurotransmitter systems involved in positive emotions and motivation, through partially dissociable mechanisms. Furthermore, the stimulating effects of nicotine and ethanol on social play behavior are independent of their anxiolytic-like properties.

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Request Reprint E-Mail: l.j.m.j.vanderschuren@umcutrecht.nl

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An IRT-based measure of alcohol trait severity and the role of traitedness in trait validity: A reanalysis of Project MATCH data

Drug and Alcohol Dependence Article in Press, 7 August 2009

With the variability among alcohol users in mind, Project MATCH hypothesized several treatment matching relationships based on alcohol severity and alcohol dependence, but found limited effects. However, it is possible that the existing examinations of Project MATCH data did not fully characterize the nature of severity of alcohol dependence, as these analyses have examined dependence severity as an additive symptom count similar to the diagnostic strategy represented in the DSM-IV.

We examined dependence severity as a latent trait hypothesized to have a characteristic developmental progression using Item Response Theory (IRT), and examined the implications of this approach to severity scaling in the Project MATCH data.

Overall, findings did not support the incremental utility of a latent trait representation of alcohol severity.

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Request Reprint E-Mail: lmorey@psych.tamu.edu

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The BRAVE (Building Resiliency and Vocational Excellence) Program: Evaluation Findings for a Career-Oriented Substance Abuse and Violence Preventive Intervention

Journal of Health Care for the Poor and Underserved - Volume 20, Number 3, August 2009, pp. 798-816

This article examines the effectiveness of a career-oriented intervention for preventing involvement with alcohol, tobacco, and other drugs (ATODs) and violence and for promoting resilient behavior among eighth-grade, African American middle school students (N=178; n=92 intervention and n=86 comparison) through the implementation of the Building Resiliency and Vocational Excellence (BRAVE) Program.

Results revealed a beneficial effect of the intervention on participants’ frequency of use of alcohol (p<.04) and marijuana (p<.05), but no effect for violent behavior.

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Request Reprint E-Mail: jgriffin@msm.edu.

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Screening and brief interventions for hazardous and harmful alcohol use in primary care: a cluster randomised controlled trial protocol

BMC Public Health 2009, 9:287

There have been many randomized controlled trials of screening and brief alcohol intervention in primary care. Most trials have reported positive effects of brief intervention, in terms of reduced alcohol consumption in excessive drinkers. Despite this considerable evidence-base, key questions remain unanswered including: the applicability of the evidence to routine practice; the most efficient strategy for screening patients; and the required intensity of brief intervention in primary care.

This pragmatic factorial trial, with cluster randomization of practices, will evaluate the effectiveness and cost-effectiveness of different models of screening to identify hazardous and harmful drinkers in primary care and different intensities of brief intervention to reduce excessive drinking in primary care patients.

The trial will evaluate the impact of screening and brief alcohol intervention in routine practice; thus its findings will be highly relevant to clinicians working in primary care in the UK. There will be an intention to treat analysis of study outcomes at 6 and 12 months after intervention. Analyses will include patient measures (screening result, weekly alcohol consumption, alcohol-related problems, public service use and quality of life) and implementation measures from practice staff (the acceptability and feasibility of different models of brief intervention.) We will also examine organisational factors associated with successful implementation.

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A Functional Polymorphism of the NFKB1 Gene Increases the Risk for Alcoholic Liver Cirrhosis in Patients With Alcohol Dependence

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-κB, the NF-κB inhibitor α (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-γ in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC.

The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC.

The deletion allele of the −94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.

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Request Reprint E-Mail: laso@usal.es

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A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone in Outpatients With Bipolar Disorder and Alcohol Dependence

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence.

In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence.

Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.

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Request Reprint E-Mail: sherwood.brown@utsouthwestern.edu

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Alcoholism and Dampened Temporal Limbic Activation to Emotional Faces

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Excessive chronic drinking is accompanied by a broad spectrum of emotional changes ranging from apathy and emotional flatness to deficits in comprehending emotional information, but their neural bases are poorly understood.

Deficient activation of amygdala and hippocampus may underlie impaired processing of emotional faces associated with long-term alcoholism and may be a part of the wide array of behavioral problems including disinhibition, concurring with previously documented interpersonal difficulties in this population. Furthermore, the results suggest that alcoholics may rely on prefrontal rather than temporal limbic areas in order to compensate for reduced limbic responsivity and to maintain behavioral adequacy when faced with emotionally or socially challenging situations.

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Request Reprint E-Mail: xenia@ucsd.edu

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Intensity and Duration of Chronic Ethanol Exposure Is Critical for Subsequent Escalation of Voluntary Ethanol Drinking in Mice

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Excessive alcohol drinking continues to be an important health problem. Recent studies from our laboratory and others have demonstrated that animal models of ethanol dependence and relapse can contribute to understanding factors that contribute to excessive drinking.

In this study, we tested the hypothesis that the amount and duration of ethanol exposure is critical for promoting the escalation in drinking by mice given access to ethanol in a limited access paradigm.

We found that the intensity (amount) and duration of ethanol exposure, indexed by BEC, is critical to produce increased drinking in mice. Specifically, BEC must regularly exceed 175 mg/dl for the escalation in drinking to occur. Future studies will examine neurobiological adaptations that may underlie the increased drinking behavior caused by chronic intermittent ethanol exposure.

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Request Reprint E-Mail: griffinw@musc.edu

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Differential Effects of Chronic Ethanol Consumption and Withdrawal on Homer/Glutamate Receptor Expression in Subregions of the Accumbens and Amygdala of P Rats

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N-methyl-d-aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse.

In this study, we examined the effects of short versus long-term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol-preferring P rats.

Overall, these subregion specific, ethanol-induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol's rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse.

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

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Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH-2 Inhibitor

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH-2 inhibitor might affect other metabolic factors involved in regulating drinking.

Our findings suggest that selective reversible ALDH-2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics.

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Request Reprint E-Mail: ivan.diamond@cvt.com

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Ethanol Inhibits Muscarinic Receptor-Induced Axonal Growth in Rat Hippocampal Neurons

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

In utero alcohol exposure can lead to fetal alcohol spectrum (FAS) disorders characterized by cognitive and behavioral deficits. In vivo and in vitro studies have shown that ethanol alters neuronal development. One mechanism through which ethanol has been shown to exert its effects is the perturbation of activated signaling cascades. The cholinergic agonist carbachol has been shown to induce axonal outgrowth through intracellular calcium mobilization, protein kinase C (PKC) activation, and ERK1/2 phosphorylation.

This study investigated the effect of ethanol on the differentiation of rat hippocampal pyramidal neurons induced by carbachol as a possible mechanism involved in the developmental neurotoxicity of ethanol.

Ethanol inhibited carbachol-induced neurite outgrowth by inhibiting PKC and ERK1/2 activation. These effects may be, in part, responsible for some of the cognitive deficits associated with in utero alcohol exposure.

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Request Reprint E-Mail: marinag@u.washington.edu

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Increased Perioculomotor Urocortin 1 Immunoreactivity in Genetically Selected Alcohol Preferring Rats

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Urocortin 1 (Ucn 1) is an endogenous peptide related to the corticotropin-releasing factor (CRF). Ucn 1 is mainly expressed in the perioculomotor area (pIII), and its involvement in alcohol self-administration is well confirmed in mice. In other species, the relationship between the perioculomotor Ucn 1-containing population of neurons (pIIIu) and alcohol consumption needs further investigation. The pIII also has a significant subpopulation of dopaminergic neurons. Because of dopamine's (DA) role in addiction, it is important to evaluate whether this subpopulation of neurons contributes to addiction-related phenotypes. Furthermore, the effects of gender on the relationship between Ucn 1 and tyrosine hydroxylase (TH) in pIII and alcohol preference in rats have not been previously assessed.

These findings extend previous reports of increased Ucn 1-positive cell distribution in preferring lines of animals. They indicate that Ucn1 contributes to increased alcohol consumption across different species and that this contribution could be gender specific. The results also suggest that Ucn1 regulates positive reinforcing rather than aversive properties of alcohol and that these effects could be mediated by CRF2 receptors, independent of direct actions of DA.

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Request Reprint E-Mail: ryabinin@ohsu.edu

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Binge Drinking Affects Attentional and Visual Working Memory Processing in Young University Students

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

Binge Drinking (BD) typically involves heavy drinking over a short time, followed by a period of abstinence, and is common among young people, especially university students. Animal studies have demonstrated that this type of alcohol consumption causes brain damage, especially in the nonmature brain.

The aim of the present study was to determine how BD affects brain functioning in male and female university students, during the performance of a visual working memory task.

The results of this study confirm the presence of electrophysiological differences between young university student binge drinkers and controls during the execution of a visual task with a high working memory load. The larger N2 in the BD group suggests higher levels of attentional effort required by this group to perform the task adequately. The absence of any differences in the P3 component in the different conditions (matching and nonmatching stimuli) in the BD group suggests a deficiency in the electrophysiological differentiation between relevant and irrelevant information, which may reflect some impairment of working memory processes.

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Request Reprint E-Mail: alberto.crego@usc.es

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Effects of Prenatal Alcohol Exposure on Brain Activation During an Arithmetic Task: An fMRI Study

Alcoholism: Clinical and Experimental Research Early View 10 Aug 2009

While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task.

Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.

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Request Reprint E-Mail: ccoles@emory.edu

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Schedule of Passive Ethanol Exposure Affects Subsequent Intragastric Ethanol Self-Infusion

Alcoholism: Clinical and Experimental Research Early View 10 August 2009

Many studies have shown that chronic ethanol exposure can enhance later self-administration of ethanol, but only a few studies have identified critical parameters for such exposure. The present studies examined temporal and other parameters of chronic ethanol exposure on subsequent intragastric (IG) self-infusion of ethanol.

Measurement of withdrawal signs indicated that Massed passive exposure produced stronger dependence than Spaced passive exposure, suggesting that enhanced ethanol self-infusion in Massed Groups might be explained by the opportunity for greater negative reinforcement by ethanol. Although enhanced negative reinforcement might also explain why the Massed Group showed a weaker aversion for the ethanol-paired flavor than the Spaced Group, this observation could also be explained by the development of greater tolerance to ethanol's aversive pharmacological effects in the Massed Group.

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Request Reprint E-Mail: fidlert@ohsu.edu

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Affective temperaments in alcoholic patients

Alcohol Volume 43, Issue 5, August 2009, Pages 397-404

Ninety-four consecutive responders to treatment alcoholics, 39 with and 55 without psychiatric comorbidity, were compared, regarding affective temperaments, according to the formulation of Akiskal and Mallya, with 50 healthy volunteers displaying the same social characteristics and belonging to the same environment.

The present study shows the main ways in which alcoholics can be distinguished from controls in terms of cyclothymic traits, with a depressive component, and why these characteristics are unrelated to the presence of dual diagnosis.

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Request Reprint E-Mail: paciland@virgilio.it

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Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus

Alcohol Volume 43, Issue 5, August 2009, Pages 387-396

Neonatal alcohol exposure produces long-term changes in the suprachiasmatic nucleus (SCN) that are presumably responsible for disturbances in the light–dark regulation of circadian behavior in adult rats, including the pattern of photoentrainment, rate of re-entrainment to shifted light–dark cycles, and phase-shifting responses to light.

Because SCN neurons containing vasoactive intestinal polypeptide (VIP) receive direct photic input via the retinohypothalamic tract and thus play an important role in the circadian regulation of the SCN clock mechanism by light, the present study examined the long-term effects of neonatal alcohol exposure on VIP neuronal populations within the SCN of adult rats.

These results demonstrate that VIP neuronal populations in the SCN are vulnerable to EtOH-induced insult during brain development. The observed alterations in SCN neurons containing VIP may have an impact upon clock responses to light input and thus contribute to the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior.

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Request Reprint E-Mail: dearnest@medicine.tamhsc.edu

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Orexin-1 receptor antagonism decreases ethanol consumption and preference selectively in high-ethanol–preferring Sprague–Dawley rats

Alcohol Volume 43, Issue 5, August 2009, Pages 379-386

Work from our laboratory has shown that orexin (ORX; or hypocretin) neurons in the lateral hypothalamus are involved in preference for morphine, cocaine, and food. Other groups have demonstrated a connection between the ORX system and ethanol-related behaviors.

Here, we extended those results to investigate, in outbred Sprague–Dawley rats, the relationship between ethanol preference and the ORX system.

These results demonstrate a strong, causal relationship between the ORX system and ethanol preference in outbred rats. These findings provide additional evidence that the ORX system provides opportunities to develop novel treatments for alcohol abuse.

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Request Reprint E-Mail: astong@musc.edu

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Sex differences in acute ethanol withdrawal severity after adrenalectomy and gonadectomy in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant mice

Alcohol Volume 43, Issue 5, August 2009, Pages 367-377

Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent γ-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals.

Thus, the goal of the present study was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines.

Overall, the increase in acute EtOH withdrawal severity in female WSP and WSR mice after adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery.

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Request Reprint E-Mail: strongm@ohsu.edu

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Opioid antagonists block the acquisition of ethanol-mediated conditioned tactile preference in infant rats

Alcohol Volume 43, Issue 5, August 2009, Pages 347-358

It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age.

The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process.

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Request Reprint E-Mail: rpautassi@gmail.com

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