The δ1 Opioid Receptor Is a Heterodimer That Opposes the Actions of the δ2 Receptor on Alcohol Intake

Biological Psychiatry Article in Press 3 July 2009

We show that the subtypes of the δ receptor, δ1 and δ2, have opposing effects on ethanol consumption. We find that these effects are synergistic; thereby suggesting that δ1 and δ2 receptors are distinct molecular targets. Indeed, we provide both in vitro as well as in vivo evidence that the δ1 subtype is a μ-δ heterodimer and that the δ2 subtype is most likely a δ homomer.

Together these data provide insight into the limited actions of the clinically important drug naltrexone and identify a novel target with improved specificity and efficacy for the development of new therapeutics for the treatment of alcoholism.

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Request Reprint E-Mail: whistler@gallo.ucsf.edu

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The Impact of Alcohol in: Greater Manchester Fourth Quarter - May 2009

This report identifies available alcohol intelligence from across Greater Manchester. The data are separated into six categories: consumption, health related impacts of alcohol, crime, young people, and examples of interventions to tackle excessive alcohol consumption. The report contains the latest annual and quarterly data available. Where no updates have been published, the latest data published in the last quarterly report is still provided here for reference. Where data are new or updated, these are labelled as such throughout this report .

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Development and validation of the Alcoholics Anonymous Intention Measure (AAIM)

Drug and Alcohol Dependence Article in Press, 5 July 2009

Drop-out from 12-step groups is notoriously high, yet the field lacks strong models and scales for addressing this problem. We aim to determine whether the theory of planned behavior (TPB) can be applied to 12-step involvement, and to develop and validate a scale of 12-step readiness based on that theory: the Alcoholics Anonymous Intention Measure (AAIM).

Results generally support the TPB as a model of 12-step involvement and suggest specific targets for 12-step facilitation interventions within attitude, norm, and control components. Findings also support the AAIM as a tool for identifying drop-out risks and tailoring individual interventions.

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Request Reprint E-Mail: szemore@arg.org

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Measuring Liability for Substance Use Disorder among College Students: Implications for Screening and Early Intervention

The American Journal of Drug and Alcohol Abuse, Volume 35, Issue 4 July 2009 , pages 233 - 241

Heavy drinking and illicit drug use among college students has been a longstanding public health concern. Current methods to screen and identify college students at-risk for the development of substance use disorders (SUD) are somewhat limited.

This study aimed to cross-validate the work by Kirisci et al., who developed the Transmissible Liability Index (TLI), by deriving a set of items that would be potentially useful for characterizing SUD risk across multiple dimensions among college students.

The TLI-CV was significantly associated with baseline dependence and significantly higher for non-dependent individuals who later became dependent during the subsequent three years of college. These associations were observed for both sexes, Whites, Blacks/African-Americans, Asians, and other racial minorities. The sensitivity and specificity were suboptimal.

The TLI-CV advances prior research to identify college students at risk for SUD. This approach holds potential promise to identify and ultimately modify the trajectories of college students who may be at risk for the development of SUD.

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Request Reprint E-Mail: aarria@cesar.umd.edu

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Genome-wide Association Study of Alcohol Dependence

Arch Gen Psychiatry. 2009;66(7):773-784.

Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder.

To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset.

This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.

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Request Reprint E-Mail: marcella.rietschel@zi-mannheim.de

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Ethanol-Modulated Camouflage Response Screen in Zebrafish Uncovers a Novel Role for cAMP and Extracellular Signal-Regulated Kinase Signaling in Behavioral Sensitivity to Ethanol

The Journal of Neuroscience, July 1, 2009, 29(26):8408-8418

Ethanol, a widely abused substance, elicits evolutionarily conserved behavioral responses in a concentration-dependent manner in vivo. The molecular mechanisms underlying such behavioral sensitivity to ethanol are poorly understood. While locomotor-based behavioral genetic screening is successful in identifying genes in invertebrate models, such complex behavior-based screening has proven difficult for recovering genes in vertebrates.

Here we report a novel and tractable ethanol response in zebrafish. Using this ethanol-modulated camouflage response as a screening assay, we have identified a zebrafish mutant named fantasma (fan), which displays reduced behavioral sensitivity to ethanol.

Positional cloning reveals that fan encodes type 5 adenylyl cyclase (AC5). fan/ac5 is required to maintain the phosphorylation of extracellular signal-regulated kinase (ERK) in the forebrain structures, including the telencephalon and hypothalamus. Partial inhibition of phosphorylation of ERK in wild-type zebrafish mimics the reduction in sensitivity to stimulatory effects of ethanol observed in the fan mutant, whereas, strikingly, strong inhibition of phosphorylation of ERK renders a stimulatory dose of ethanol sedating.

Since previous studies in Drosophila and mice show a role of cAMP signaling in suppressing behavioral sensitivity to ethanol, our findings reveal a novel, isoform-specific role of AC signaling in promoting ethanol sensitivity, and suggest that the phosphorylation level of the downstream effector ERK is a critical "gatekeeper" of behavioral sensitivity to ethanol.

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Request Reprint E-Mail: su.guo@ucsf.edu

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Persistent Deficits in Heart Rate Response Habituation Following Neonatal Binge Ethanol Exposure

Alcoholism: Clinical and Experimental Research1 Published Online: 10 Jun 2009

These data suggest that there are relatively long-term consequences of neonatal ethanol exposure on nonassociative memory. This impairment in habituation may be relevant to the distractibility and poor focused attention that is pervasive among humans diagnosed with fetal alcohol spectrum disorders.

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Request Reprint E-Mail: pshunt@wm.edu

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Alcohol Abuse Enhances Pulmonary Edema in Acute Respiratory Distress Syndrome

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Pulmonary edema is a cardinal feature of the life-threatening condition known as acute respiratory distress syndrome (ARDS). Patients with chronic alcohol abuse are known to be at increased risk of developing and dying from ARDS.

Based upon preclinical data, we hypothesized that a history of chronic alcohol abuse in ARDS patients is associated with greater quantities and slower resolution of pulmonary edema compared with ARDS patients without a history of alcohol abuse.

In patients who develop ARDS, alcohol abuse is associated with greater levels EVLW and a trend towards slower resolution of EVLW. Combined with mechanistic and preclinical evidence linking chronic alcohol consumption and ARDS, targeted therapies should be developed for these patients.

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Request Reprint E-Mail: greg.martin@emory.edu

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Upregulation of Serotonin Transporter by Alcohol in Human Dendritic Cells: Possible Implication in Neuroimmune Deregulationical
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Our study suggests that alcohol upregulates SERT and MAO-A by elevating cyclic AMP, which may lead to decreased concentration of 5-HT in the extracellular medium. As 5-HT is a major neurotransmitter and an inflammatory mediator, its alcohol-mediated depletion may cause both neurological and immunological deregulation.

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Request Reprint E-Mail: nairm@fiu.edu
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Alcohol-Induced Electrical Remodeling: Effects of Sustained Short-Term Ethanol Infusion on Ion Currents in Rabbit Atrium

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

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Request Reprint E-Mail: roman.laszlo@med.uni-tuebingen.de

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Modulation of Brain Endocannabinoid Levels by Voluntary Alcohol Consumption in Alcohol-Preferring AA Rats

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

These results demonstrate that voluntary alcohol drinking modulates the levels of endocannabinoids in several brain areas implicated in alcohol reinforcement. AEA and 2-AG were differentially affected, suggesting that they could have partially separate modulatory roles. Alterations were more widespread in females than males, possibly reflecting their higher alcohol intake. Taken together, alcohol-induced release of endocannabinoids may have an important role in alcohol reinforcement and development of alcohol addiction.

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Request Reprint E-Mail: petri.hyytia@thl.fi

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A Single, Moderate Ethanol Exposure Alters Extracellular Dopamine Levels and Dopamine D2 Receptor Function in the Nucleus Accumbens of Wistar Rats
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

The present results indicate that a single EtOH pretreatment at a moderate dose can increase DA neurotransmission in the NAc due, in part, to reduced D2 autoreceptor function.

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Request Reprint E-Mail: jmurphy1@iupui.edu
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Reduction of Alcohol's Reinforcing and Motivational Properties by the Positive Allosteric Modulator of the GABAB Receptor, BHF177, in Alcohol-Preferring Rats
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

The present results extend to BHF177 the capacity of the 2 previously tested positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, to specifically suppress alcohol's reinforcing and motivational properties in alcohol-preferring rats.

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Rerquesty Reprint E-Mail: colomb@unica.it
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Social–cognitive correlates of protective drinking behaviors and alcohol-related consequenes in college students

Addictive Behaviors Article in Press 27 May 2009

Although heavy episodic drinkers are at risk to experience alcohol-related consequences, studies show that a large percentage of student drinkers do not experience problems as a result of their drinking.

The present study was a more in-depth examination of factors beyond just drinking quantity and frequency to explain why students experience consequences. The current research examined the relationship between the use of protective behaviors, alcohol use, and alcohol related consequences, as well as the relationship between attitudinal and cognitive predictors of engaging in protective behaviors when drinking.

We hypothesized there would be a significant direct effect of protective behaviors on consequences after taking into account the effect of alcohol use and that cognitive predictors, including perceived self-efficacy, perceived effectiveness, and subjective norm, would be associated with the attitude and frequency of engaging in protective behaviors.

Results supported both hypotheses, indicating good model fit for all models and significant paths between constructs .

These findings extend the literature on protective behaviors by providing insight as to their utility in preventing harm and why students choose to engage in these behaviors. Implications for interventions are also discussed.

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Request Reprint E-Mail: anneray@psu.edu

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Study of Implementation of a Guideline for Brief Alcohol Intervention in Primary Care.

Journal of Nursing Care Quality Publish Ahead of Print, 1 July 2009

Application of research findings to clinical care has been advocated to improve quality of care and patient outcomes. This article discusses a method to evaluate the translation of research findings in support of evidence-based care. An exemplar of a brief intervention in primary care for high-risk drinkers is used.

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Request Reprint E-Mail: zhyman@daemen.edu

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Internationally recognized guidelines for ‘sensible’ alcohol consumption: is exceeding them actually detrimental to health and social circumstances? Evidence from a population-based cohort study

Journal of Public Health Advance Access published online on July 2, 2009

In the present study, there was some evidence for a detrimental effect on health and social circumstances of exceeding current internationally recognized weekly and daily guidelines for alcohol intake on selected health and social outcomes.

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Request Reprint E-Mail: david-b@sphsu.mrc.ac.uk

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The Road to Recovery: Where Are We Going and How Do We Get There? Empirically Driven Conclusions and Future Directions for Service Development and Research

Substance Use & Misuse, Volume 43, Issue 12 & 13 October 2008 , pages 2001 - 2020

The term “recovery” is often used in the addiction field. However, we have thus far failed to define the term, to delineate its dimensions, or to elucidate the prerequisite conditions to this outcome. This has hindered service development and evaluation as well as changes in policy.

This paper:

• Reviews empirical findings about how “recovery” is defined and experienced by individuals engaged in the process;


• 
  Examines factors associated with recovery initiation, maintenance, and sustained lifestyle, and review obstacles to recovery; and


• 
  Discusses implications for services and research; implications include the need to adopt a long-term, wellness-centered approach to addressing substance use related problems, the importance for society to address the stigma of former addiction and to offer attractive viable opportunities to promote making significant life changes toward recovery from substance use.

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Request Reprint E-Mail: laudet@ndri.org

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Initial National Priorities for Comparative Effectiveness Research

REPORT BRIEF • JUNE 2009

The American Recovery and Reinvestment Act of 2009 called on the Institute of Medicine to recommend a list of priority topics to be the initial focus of a new national investment in comparative effectiveness research. The IOM’s recommendations are contained in the report, Initial National Priorities for Comparative Effectiveness Research. The list of priority topics is provided below. The topics are listed by quartile (groups of 25). The first quartile is considered the highest priority group and the fourth quartile the lowest. Within each group, however, the order of individual topics does not indicate rank.

The list provides a starting point for what the report says should be a sustained effort to conduct comparative effectiveness research. As this research initiative progresses, the priorities will evolve as well. Ultimately, research on these and future topics will not yield real improvements unless the results are adopted by health care providers and organizations and integrated into clinical practice.

Fourth Quartile

• Compare the effectiveness of traditional behavioral interventions versus economic incentives in motivating behavior changes (e.g., weight loss, smoking cessation, avoiding alcohol and substance abuse) in children and adults.

100 Initial Priority Topics for Comparative Effectiveness Research

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Rethinking Drinking

For anyone who drinks, Rethinking Drinking offers valuable, research-based information. The first part, How much is too much?, answers these questions and more:

• What’s "low-risk" drinking versus "at-risk" or "heavy" drinking?

• Why is being able to "hold your liquor" a concern?

• What are signs that drinking is causing harm?

Many heavy drinkers do not have alcohol-related problems yet and can reduce their risk of harm by cutting back. For the nearly 18 million Americans who have alcoholism or related problems, however, it’s safest to quit.

The second part of this booklet, Thinking about a change?, offers tips, tools, and resources for people who choose to cut down or quit. Success is likely for those who persist in their efforts. Even for those with alcoholism, studies show that most do recover, often without professional treatment

What do you think about taking a look at your drinking habits and how they may affect your health? Rethinking Drinking can help you get started.

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Rethinking Drinking website
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Decreased Amygdala Activation during Risk Taking in Non-Dependent Habitual Alcohol Users: A Preliminary fMRI Study of the Stop Signal Task

The American Journal of Drug and Alcohol Abuse Published Online 2 July 2009



Habitual alcohol use is prodromal to alcohol dependence. It has been suggested that impairment in impulse control contributes to habitual drinking. Little is known whether neural processes associated with impulse control is altered in non-dependent social drinkers. The current preliminary study combined functional magnetic resonance imaging and the stop signal task (SST) to address this issue.

We showed that moderate/heavy alcohol drinkers were decreased in amygdala activation during risk taking, while indistinguishable in neural measures of inhibitory control, when compared to non/light drinkers.

Altered amygdala activation during risk taking may be a key neural process underlying early habitual alcohol use and a potential marker mediating transition to alcohol dependence.

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Request Reprint E-Mail: chiang-shan.li@yale.edu
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Alcohol dependence–related increase of glial cell density in the anterior cingulate cortex of suicide completers

J Psychiatry Neurosci 2009;34(4):281-8.

Glial densities, neuronal densities and soma sizes measured in BA24a did not differ significantly between controls and suicide completers. Secondary analyses showed a significant and robust increase in glial cell densities in BA24a of alcohol-dependent depressed suicide completers compared with depressed suicide completers who were not alcohol-dependent (38%) and, to a lesser extent, controls (30%).

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Alcohol consumption and use of acute and mentalhealth hospital services in the West of ScotlandCollaborative prospective cohort study J Epidemiol Community Health. Published Online First: 1 July 2009.

Men who consumed 22 or more units per week had a 20% higher rate of acute admissions than nondrinkers. The number of bed-days were higher for men drinking eight or more units and increased with consumption, with the highest category having a 58% higher rate of bed-days than non-drinkers. Non-drinkers had the highest admissions for CHD.

For stroke, drinkers of 15 or more units had higher admissions and higher number of bed-days and these increased with increasing consumption. Respiratory admissions were higher for drinkers of 22 or more units and bed-days were higher fordrinkers of 15 or more units. Alcohol-related admissions and number of bed-days generally increased with consumption.
Mental health admissions and number of bed-days were raised for drinkers of 22 or more units with a suggestion of a J-shaped relationship.

Alcohol consumption has a substantial effect on acute and mental health admissions and bed-days.

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Request Reprint E-Mail: c.l.hart@udcf.gla.ac.uk



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NEUROSCIENCE: PATHWAYS TO ALCOHOL DEPENDENCE

Alcohol Alerts No. 77 April 2009

Today, thanks to rapidly advancing technology, researchers know more than ever about how alcohol affects the brain and how the brain responds and adapts to these effects. This Alcohol Alert summarizes some of what we know about alcohol’s short- and long-term effects on the brain and how breakthroughs in neuroscience are leading to better treatments for alcohol-related problems.

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Epidemiology of Alcohol Abuse and Dependence in Rural Chinese Men

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Alcohol abuse and dependence are no longer uncommon disorders among rural men in China. Unlike most western reports, alcohol dependence shows higher prevalence than abuse. There are significant differences in the prevalence of alcohol use disorders and the socio-demographic profile of affected individuals in the 2 different regions of the country.

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Request Reprint E-Mail: zhouliang@xysm.net

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Association of self-reported alcohol use and hospitalization for an alcohol-related cause in Scotland: a record-linkage study of 23 183 individuals

Addiction, Volume 104, Number 4, April 2009 , pp. 593-602(10)

Moderate and higher levels of usual alcohol consumption and binge drinking are serious risk factors for alcohol-related hospitalization in the Scottish population. These findings contribute to our understanding of the relationship between alcohol intake and alcohol-related morbidity

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Request Reprint E-Mail: scott.mcdonald@hps.scot.nhs.uk

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Young Adults' Need for and Receipt of Alcohol and Illicit Drug Use Treatment: 2007

In the past year, about one fifth of young adults aged 18 to 25 (21.1 percent) needed treatment for alcohol or illicit drug use, but less than one tenth (7.0 percent) of them received treatment at a specialty facility. Of the young adults who needed but did not receive alcohol or illicit drug use treatment in a specialty facility in the past year, 96.0 percent did not perceive the need for treatment.

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Early Release of Selected Estimates Based on Data From the 2008 National Health Interview Survey

9. Alcohol consumption PDF Version

• Figure 9.1. Percentage of adults aged 18 years and over who had five or more drinks in 1 day at least once in the past year: United States, 1997-2008
  
• Figure 9.2. Percentage of adults aged 18 years and over who had five or more drinks in 1 day at least once in the past year, by age group and sex: United States, 2008
  
• Figure 9.3. Age-sex-adjusted percentage of adults aged 18 years and over who had five or more drinks in 1 day at least once in the past year, by race/ethnicity: United States, 2008
  
• Data tables for Figures 9.1-9.3

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Alcohol and Drug Use Before and During Pregnancy: An Examination of Use Patterns and Predictors of Cessation

Maternal and Child Health Journal Volume 13, Number 3 / May, 2009 pp. 386-394

Women who continued to use alcohol or drugs after learning they were pregnant were more frequent users than spontaneous quitters, more likely to smoke cigarettes, and had more psychosocial stressors. Achieving higher rates of cessation may require approaches that simultaneously address substance use and impediments to quitting. Higher continuation rates among some cultural groups require further investigation.

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Request Reprint E-Mail: pat.harrison@ci.minneapolis.mn.us

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Racial Disparities in Pregnancy-Related Drinking Reduction

Maternal and Child Health Journal Published Online September 09, 2008

Significant racial differences in pregnancy-related drinking reduction are evident, and may help explain racial disparities in FAS. Results suggest that more targeted efforts are needed to meet the national goals of preventing alcohol-exposed pregnancies.

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Request Reprint E-Mail: tenkku@slu.edu

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Preliminary Evaluation of Phosphatidylethanol and Alcohol Consumption in Patients with Liver Disease and Hypertension
Alcohol and Alcoholism Advance Access published online on June 17, 2009

Results support PEth measurement by HPLC-MS/MS as a promising marker of past 1- to 2-week moderate to heavy alcohol consumption in patients with and without liver disease. PEth appears useful for differentiating abstinence or light drinking from moderate to heavy consumption, but may have limited utility for differentiating moderate from heavy alcohol use.

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Request Reprint -Mail: stewarsh@musc.edu
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Osteopenia in Alcoholics: Effect of Alcohol Abstinence

Alcohol and Alcoholism Advance Access published online on June 17, 2009

Ethanol consumption leads to osteopenia, and decreased serum osteocalcin, which improve with abstinence, whereas those who continue drinking show a worsening of both parameters.

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Request Reprint E-Mail: egonrey@ull.es

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Impaired Emotional Facial Expression Decoding in Alcoholism is Also Present for Emotional Prosody and Body Postures

Alcohol and Alcoholism Advance Access published online on June 17, 2009

We observed for the first time a generalized emotional decoding impairment in alcoholism, as this impairment is present not only for faces but also for other visual (i.e. body postures) and auditory stimuli.

Moreover, we report that this alteration (1) is mainly indexed by an overestimation of anger and (2) cannot be explained by an ‘affect labelling’ impairment, as the semantic comprehension of written emotional scenarios is preserved. Fundamental and clinical implications are discussed.

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Request Reprint E-Mail: pierre.maurage@uclouvain.be

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Correlates of intensive alcohol and drug use in men who have sex with men in Catalonia, Spain

The European Journal of Public Health Advance Access published online on June 29, 2009

The high percentage of MSM who use alcohol and drugs before and during sex and association between these substances and sexual risk behaviours reveals the need to intensify interventions to reduce their levels of use and/or to reduce the associated damage and risks. These programs must try to cover MSM-specific psychosocial aspects and include prevention for HIV-positive men.

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Request Reprint E-Mail: cft.ceescat.germanstrias@gencat.cat

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Changes in alcohol consumption and drinking patterns during 11 years of follow-up among ageing men: the FinDrink study

The European Journal of Public Health Advance Access published online on June 26, 2009

Finnish men born in 1926–1946 do not seem to decrease drinking while ageing. In contrast those born in 1944–1946 increase drinking until their 60’s. This should be taken into consideration in planning health services for aged men in the near future.

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Request Reprint E-Mail: jenni.ilomaki@uku.fi

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Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial
Alcohol Volume 43, Issue 4, June 2009, Pages 259-264

Alcohol has been suggested to be a risk factor for opioid-dependent patients in methadone maintenance treatment (MMT). Literature shows that MMT has limited effects on alcohol use. Nevertheless, a decrease in alcohol use was detected in the Swiss heroin-assisted treatment (HAT) study.

In this article, we carry out an in-depth analysis of the German HAT trial with the aim of determining whether alcohol use was affected among patients undergoing HAT and MMT.

Results suggest significant reduction of CU and CDT in both groups, yet larger effects in the HAT group. ASI CS significantly decreased in the HAT but not in the MMT group. The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion.

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Request Reprint E-Mail: haasen@uke.uni-hamburg.de
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Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence
Alcohol Volume 43, Issue 4, June 2009, Pages 265-269

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to be related to neuroprotection in cell culture and animal studies. Our aim was to verify the changes in human plasma BDNF and NGF concentrations induced by chronic alcohol use.

Mean plasma BDNF level was significantly higher in the patients with alcohol dependence compared with the healthy subjects . Mean plasma NGF level was also significantly higher in patients with alcohol dependence than in healthy subjects Plasma BDNF and NGF levels showed significant negative correlation in alcohol dependence group .

Increased plasma BDNF and NGF with negative correlation in alcohol-dependent patients may have some role in the regeneration of damage done by chronic alcohol use.

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Request Reprint E-Mail: ihngeun@hallym.or.kr
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The TaqI A DRD2 polymorphism in type II alcohol dependence: a marker of age at onset or of a familial disease?
Alcohol Volume 43, Issue 4, June 2009, Pages 271-275

Cloninger's type II is a severe, early-onset, male-limited, and genetically influenced, impulsive form of alcoholism. Significant association has been reported between the A1 allele of the D2 dopamine receptor (DRD2) gene, substance misuse and personality traits of impulsivity and novelty seeking.

We assessed the association between the TaqI A DRD2 gene polymorphism with Cloninger's typology and family history of alcohol abuse, which is thought to be more frequent in type II alcoholics.

Although typology was not associated with the studied polymorphism, a higher rate of general family history of alcohol abuse was still observed in type II patients . Furthermore, the A1 allele of the DRD2 was significantly associated with paternal history of alcoholism and male, first-degree, collateral history of alcoholism .

Age at onset of alcohol-related problems as main discriminator between type I and type II alcohol dependence does not seem to be associated by the TaqI A DRD2 polymorphism. However, the A1 allele of the DRD2 may be a marker of male familial alcoholism, which has been associated with type II alcohol dependence.

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Request Reprint E-Mail: epinto@chu.ulg.ac.be
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Ethanol increases desensitization of recombinant GluR-D AMPA receptor and TARP combinations

Alcohol Volume 43, Issue 4, June 2009, Pages 277-284

Glutamate receptors are important target molecules of the acute effect of ethanol. We studied ethanol sensitivity of homomeric GluR-D receptors expressed in human embryonic kidney 293 cells and examined whether recently discovered transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory proteins (TARPs) affect ethanol sensitivity.

The results support the idea that increased desensitization is an important mechanism in the ethanol inhibition of AMPA receptors and indicate that coexpression of TARPs can alter this effect of ethanol.

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Request Reprint E-Mail: esa.korpi@helsinki.fi

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Role of the nNOS gene in ethanol-induced conditioned place preference in mice

Alcohol Volume 43, Issue 4, June 2009, Pages 285-291

Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) has a role in synaptic plasticity, and evidence suggests its role in a range of effects produced by alcohol in the central nervous system. The aim of the current study was to investigate the role of the nNOS gene in the development of ethanol-induced conditioned place preference (CPP) in mice.

Results show that both WT and nNOS KO mice developed significant CPA. The findings that the absence of the nNOS gene impaired ethanol-induced CPP but not LiCl-induced CPA suggest that NO signaling has a specific role in processing the motivational effect of ethanol. Hence, inhibition of nNOS may attenuate the development of maladaptive behaviors associated with alcohol exposure.

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Request Reprint E-Mail: yitzhak@med.miami.edu

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The heritability of P300 amplitude in 18-year-olds is robust to adolescent alcohol use

Psychophysiology Published Online: 22 Jun 2009

P3 amplitude reduction (P3AR) is associated with adolescent alcohol use (AAU) and highly heritable, suggesting that P3AR may index a genetic predisposition (e.g., an endophenotype) for AAU. However, because P3AR and AAU covary naturally in the population, these observations are also consistent with P3AR reflecting neurotoxic effects of AAU on the developing adolescent brain.

In this report, we describe the use of recent advancements in biometric modeling to examine changes in the genetic and environmental contributions to variability in P3 amplitude related to cumulative AAU by late adolescence in a large community-based twin sample.

We found that the genetic and environmental contributions to variability in P3 amplitude were unaffected by AAU. This suggests that P3AR indexes risk for alcoholism independent of any deleterious effect of AAU on adolescent brain development.

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Request Reprint E-Mail: perlm034@umn.edu

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Decreased somatostatin is related to the hypersensitivity of intestinal epithelia to LPS via upregulated TLR4–TBK1 pathway in rats chronically exposed to ethanol

Alcohol Volume 43, Issue 4, June 2009, Pages 293-303

Chronic alcoholics are predisposed to the development of a systemic inflammatory response syndrome, which is usually triggered in the gut. This study aimed to investigate in rats the role of intestinal epithelial inflammatory responsiveness in the susceptibility of alcoholics to excessive inflammation.

These findings suggest that impairment of intestinal SST production by chronic ethanol administration leading to upregulation of the TLR4–TBK1 pathway may be one of the mechanisms underlying the LPS hypersensitivity of intestinal epithelia.

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Request Reprint E-Mail: cwtang@medmail.com.cn

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