Alcohol, Other Drugs, and Health: Current Evidence

 

Current Issue: July–August 2010

Interventions and Assessments

• Can a Single Question Detect Drug Use and Drug Use Disorders?
• Brief Interventions May Increase Entry into Specialty Addiction Treatment
• Patients with HIV infection and Opioid Use Who Receive Methadone Maintenance Are More Likely to Initiate and Adhere to Antiretroviral Therapy
• Promoting Access to Hepatitis C Treatment via Integration with Methadone Maintenance Programs
• Effect of Opioid Agonist Treatment on Survival and Cessation among Patients with Injection Drug Use
• Does Naltrexone Treatment for Alcohol Disorders Reduce Health-Care Costs?
• Methadone Treatment Reduces Overall Health-Care Costs for Commercially Insured Patients with Opioid Dependence
• Effectiveness of Opioid-Treatment Agreements and Urine Testing in Reducing Opioid Misuse among Patients with Chronic Noncancer Pain

Health Outcomes

• Misuse and Diversion of Methadone and Buprenorphine Are Increasing, but Buprenorphine Appears to Have a Better Safety Profile
• Sustained Virologic Response in Hepatitis C Treatment May be Similar for Patients Who Drink Alcohol and Those Who Abstain
• Does Early Cannabis Use Lead to Psychosis?
• Cutaneous Necrosis, Purpura, and Neutropenia: Think Contaminated Cocaine
• Prescription Opioid Abuse and Dependence Increases as Younger Nonmedical Users Grow Older
• Alcohol Consumption Is Associated with Other Healthy Lifestyle Factors
• Effects of Alcohol Intake on Mortality among Older Adults

Slide Presentations

• Update on Alcohol, Other Drugs, and Health
• Journal Club 
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• Read Full Newsletter   (PDF)

NIAAA 40th Anniversary Symposium – October 4, 2010

This year marks a major milestone for NIAAA—40 years of supporting alcohol-related research and working to improve public health. NIAAA will commemorate this landmark event by hosting a special 40th Anniversary Symposium.

Join us as we review the current state of alcohol research and explore the future of the field.

NIAAA 40th Anniversary Symposium

AGENDA

October 4, 2010, 9:00 AM – 3:30 PM
5635 Fishers Ln, Terrace Level
Bethesda, MD 20852

9:00 – 9:15	Introduction	Kenneth R. Warren, Ph.D.
PANEL 1
9:15 – 9:45	Genetic Research: Who is at Risk For Alcoholism?	Tatiana Foroud, Ph.D. Indiana University School of Medicine
9:45 – 10:15	Neuroscience of Alcohol Abuse	Edith V. Sullivan, Ph.D. Stanford University School of Medicine
10:15 – 10:30	Break
10:30 – 11:00	Fetal Alcohol Spectrum Disorders	Jennifer Thomas, Ph.D. San Diego State University
11:00 – 11:30	Preventing Alcohol-Related Problems Through Policy Research	Robert B. Voas, Ph.D. Pacific Institute for Research and Evaluation
11:30 – 12:00	Panel Discussion
12:00 – 12:45	Lunch
PANEL 2
12:45 – 1:15	Alcohol, Immunity, and Health	Pranoti Mandrekar, Ph.D. University of Massachusetts Medical Center
1:15 – 1:45	Drinking, Binge Drinking, and Associated Consequences Among U.S. Ethic Minorities	Raul Caetano, M.D., Ph.D. University of Texas School of Public Health
1:45 – 2:00	Break
2:00 – 2:30	Reducing Underage and Young Adult Drinking	Michael Windle, Ph.D. Emory University
2:30 – 3:00	Focus on Comorbid Mental Health Disorders	Robert M. Anthenelli, M.D. University of Cincinnati College of Medicine Cincinnati Veterans Affairs Medical Center
3:00 – 3:30	Panel Discussion
3:30	Wrap up	Kenneth R. Warren, Ph.D.

The impact of introducing a minimum price on alcohol in Britain

In this Briefing Note, we use detailed data on the grocery shopping of more than 25,000 households during 2007 to provide descriptive evidence of alcohol purchases from supermarkets and other off-licensed premises retailers. 

We calculate the impact of a 45p per unit minimum price and describe how different households and retailers would be affected. Our calculations are based on a number of assumptions about consumer and firm behaviour which we discuss; more precise estimates would require estimation of a detailed model of household purchasing and firm pricing decisions. Our figures are based on a sample of households from Great Britain and we consider a minimum price that is applied nationally. 

We estimate that if a policy like this were rolled out across Britain it could transfer £700 million from alcohol consumers to retailers and manufacturers. This contrasts to increases in alcohol taxes, which largely result in transfers to government in the form of much needed tax revenue.

In the long-term, it would be desirable to restructure alcohol taxes so that they were based on alcohol strength, thus allowing the tax system to mimic the impact of a minimum price but ensuring the additional revenues went to the Government rather than firms. 

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Alcohol expectancy changes over a 12-week cognitive–behavioral therapy program are predictive of treatment success

This study examines if outcome expectancies (perceived consequences of engaging in certain behavior) and self-efficacy expectancies (confidence in personal capacity to regulate behavior) contribute to treatment outcome for alcohol dependence.  Few clinical studies have examined these constructs.

The Drinking Expectancy Profile (DEP), a psychometric measure of alcohol expectancy and drinking refusal self-efficacy, was administered to 298 alcohol-dependent patients (207 males) at assessment and on completion of a 12-week cognitive–behavioral therapy alcohol abstinence program.

Baseline measures of expectancy and self-efficacy were not strong predictors of outcome. However, for the 164 patients who completed treatment, all alcohol expectancy and self-efficacy factors of the DEP showed change over time. The DEP scores approximated community norms at the end of treatment. 

Discriminant analysis indicated that change in social pressure drinking refusal self-efficacy, sexual enhancement expectancies, and assertion expectancies successfully discriminated those who successfully completed treatment from those who did not. 

Future research should examine the basis of expectancies related to social functioning as a possible mechanism of treatment response and a means to enhance treatment outcome.


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Request Reprint E-Mail:   r.young@qut.edu.au

The Obsessive Compulsive Drinking Scale Is a Valid Measure of Alcohol Craving in Young Adults

Alcohol craving is associated with greater alcohol-related problems and less favorable treatment prognosis. The Obsessive Compulsive Drinking Scale (OCDS) is the most widely used alcohol craving instrument. The OCDS has been validated in adults with alcohol use disorders (AUDs), which typically emerge in early adulthood. 

This study examines the validity of the OCDS in a nonclinical sample of young adults.

Three hundred and nine college students (mean age of 21.8 years, SD = 4.6 years) completed the OCDS, Alcohol Use Disorders Identification Test (AUDIT), and measures of alcohol consumption. Subjects were randomly allocated to 2 samples. Construct validity was examined via exploratory factor analysis (n = 155) and confirmatory factor analysis (n = 154). Concurrent validity was assessed using the AUDIT and measures of alcohol consumption. A second, alcohol-dependent sample (mean age 42 years, SD 12 years) from a previously published study (n = 370) was used to assess discriminant validity.

A unique young adult OCDS factor structure was validated, consisting of Interference/Control, Frequency of Obsessions, Alcohol Consumption and Resisting Obsessions/Compulsions. 

The young adult 4-factor structure was significantly associated with the AUDIT and alcohol consumption. 

The 4 factor OCDS successfully classified nonclinical subjects in 96.9% of cases and the older alcohol-dependent patients in 83.7% of cases. Although the OCDS was able to classify college nonproblem drinkers (AUDIT <13, n = 224) with 83.2% accuracy, it was no better than chance (49.4%) in classifying potential college problem drinkers (AUDIT score ≥13, n = 85).

Using the 4-factor structure, the OCDS is a valid measure of alcohol craving in young adult populations. In this nonclinical set of students, the OCDS classified nonproblem drinkers well but not problem drinkers. 

Studies need to further examine the utility of the OCDS in young people with alcohol misuse.


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Request Reprint E-Mail:   

Gerald_Feeney@health.qld.gov.au

A Comparison of Methods for Estimating Change in Drinking following Alcohol Treatment

The ultimate goal of alcohol treatment research is to develop interventions that help individuals reduce their alcohol use. 

To determine whether a treatment is effective, researchers must then evaluate whether a particular treatment affects changes in drinking behavior after treatment. Importantly, drinking following treatment tends to be highly variable between individuals and within individuals across time.

Using data from the COMBINE study (COMBINE Study Group, 2003), the current study compared 3 commonly used and novel methods for analyzing changes in drinking over time: latent growth curve (LGC) analysis, growth mixture models, and latent Markov models.

Specifically, using self-reported drinking data from all participants (n = 1,383, 69% male), we were interested in examining how well the 3 estimated models were able to explain observed changes in percent heavy drinking days during the 52 weeks following treatment.

The results from all 3 models indicated that the majority of individuals were either abstinent or reported few heavy drinking days during the 52-week follow-up and only a minority of individuals (10% or fewer) reported consistently frequent heavy drinking following treatment.

All 3 models provided a reasonably good fit to the observed data with the latent Markov models providing the closest fit. 

The observed drinking trajectories evinced discontinuity, whereby individuals seem to transition between drinking and nondrinking across adjacent follow-up assessment points. 

The LGC and growth mixture models both assumed continuous change and could not explain this discontinuity in the observed drinking trajectories, whereas the latent Markov approach explicitly modeled transitions between drinking states.
 

The 3 models tested in the current study provided a unique look at the observed drinking among individuals who received treatment for alcohol dependence. 

Latent Markov modeling may be a highly desirable methodology for gaining a better sense of transitions between positive and negative drinking outcomes.


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Request Reprint E-Mail: katie.witkiewitz@wsu.edu  

Aversive Effects of Ethanol in Adolescent Versus Adult Rats: Potential Causes and Implication for Future Drinking

Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors.

The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual.

Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. 

In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol’s physiologic effects?

Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs).

We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. 

Adolescents also exhibited a greater increase in consumption after deprivation than adults. 

Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs.

These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors.

These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol.


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Request Reprint E-Mail: Nicole.schrammsapyta@duke.edu  

Do Smooth Waters Run Deep? Alcohol Intoxication and the Effects of Water Consumption on Driving-Related Cognitions and Behavior

The present study tested the effect of the combined use of alcohol and water on driving-related cognitions and behavior. 

Seventy-four female students performed a driving simulator task after having consumed alcohol or a placebo. Additionally, half of the participants consumed 0.5 liter of water.

It was hypothesized that combining alcohol and water could lead to an underestimated perceived intoxication level resulting in more favorable driving cognitions and increased risk behavior.

Our findings showed that the combined use of water and alcohol did not affect cognitions or behavior.

Surprisingly, in the placebo condition, water intake increased risky driving cognitions and behavior in women with a history of accident involvement.

Lacking a clear counterproductive effect when combined with alcohol, water could be a useful tool in limiting alcohol use among female drinkers.

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Request Reprint E-Mail: 

n.spijkerman@pwo.ru.nl

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Alcohol News - 39/2010

Scotsman (Finland) - Finnish experience suggests price can have strong effect
THE Finnish experience is one which has influenced opinion- formers who have argued vociferously that the price of alcohol has a strong effect on consumption. In Finland, tax on alcohol was cut six years ago, leading to price reductions of up to a third, depending on the type of alcohol.
http://news.scotsman.com/politics/Finnish-experience-suggests-price-can.6546213.jp

Estonian Public Broadcasting (Estonia) - The Vodka Diaries
Are Estonia's policymakers aware that their country has a drinking problem? When you think of a drunk, a certain image may come to mind. Maybe he has rosy cheeks, a scruffy white beard, and a mouth half full of yellow teeth. But living in Estonia, I have seen all kinds of drunks: young kids in tracksuits, old men in rags, round ladies with bad haircuts.
http://news.err.ee/opinion/45582dbf-aa7a-451c-9b9b-85b1661dc1c0

U.S. News & World Report (USA) - Pediatricians Want to Restrict Ads for Tobacco, Booze, Viagra
The American Academy of Pediatrics doesn't want children exposed to tobacco ads at all, and wants to limit their exposure to alcohol marketing and advertisements for erectile dysfunction drugs and other prescription medications.
http://health.usnews.com/health-news/family-health/childrens-health/articles/2010/09/27/pediatricians-want-to-restrict-ads-for-tobacco-booze-viagra.html

Medical News Today - Frequent Family Dinners Linked To Lower Tobacco, Alcohol And Marijuana Use Among Teens
American teenagers who regularly have family dinners are much less likely to have used drugs, alcohol or marijuana compared to their peers who have family dinners infrequently, according to a new study - The Importance of Family Dinners VI - carried out by researchers from The National Center on Addiction and Substance Abuse (CASA), Columbia University.
http://www.medicalnewstoday.com/articles/202601.php

Philippine Information Agency (Philippines) - Doctors group back higher 'sin' taxes for tobacco, alcohol
The Philippine Medical Association (PMA) through its President Oscar D. Tinio, M.D. expressed full support to President Benigno Aquino III's call for higher 'sin' taxes to generate additional tax revenue for the government.
http://www.pia.gov.ph/?m=12&r=&y=&mo=&fi=p100927.htm&no=32

Private Healthcare UK - Alcohol recovery 'impacted by stress'
High levels of a stress hormone could be having a negative impact on recovering alcoholics.
http://www.privatehealth.co.uk/news/september-2010/alcohol-recovery-impacted-by-stress-32938/

Voxy (Australia) - De-Normalisation - How To Reduce Alcohol Harm Amongst Young People
Research just published in the Australian and New Zealand Journal of Psychiatry shows there are six things that parents can do to reduce the risk of alcohol related harm in their children. These include: - not getting intoxicated in front of them; - not supplying them with alcohol.
http://www.voxy.co.nz/national/de-normalisation-how-reduce-alcohol-harm-amongst-young-people/5/65037

BusinessWeek - Booze Tax Hikes May Reduce Alcohol-Related Problems
Boosting taxes on alcohol leads to lower rates of alcohol-related disease, injury, death and crime, researchers say.
http://www.businessweek.com/lifestyle/content/healthday/643437.html

Chicago Sun-Times - A little alcohol staggers older drinkers
Older people who have had a couple of cocktails may still be under the legal blood-alcohol limit, but researchers have found some have trouble in walking tests.
http://www.suntimes.com/news/nation/2745140,CST-NWS-drink26.article

7thSpace Interactive - The association between intimate partner violence, alcohol and depression in family practice
Depressive symptoms, intimate partner violence and hazardous drinking are common among patients attending general practice. Despite the high prevalence of these three problems; the relationship between them remains relatively unexplored.
http://7thspace.com/headlines/358471/the_association_between_intimate_partner_violence_alcohol_and_depression_in_family_practice__.html

Richmond Times Dispatch (USA) - VCU report on privatization: increase taxes on alcohol
If Virginia sells its liquor monopoly, the state should take steps to discourage excessive drinking, including raising taxes on alcohol to reduce demand, according to a new report by Virginia Commonwealth University.
http://www2.timesdispatch.com/news/virginia-politics/2010/sep/23/vabc23-ar-520432/

PR Newswire(USA) - MADD Marks 30th Anniversary With Capitol Hill Rally Unveiling Tech-Based MADD 3.0 Action Plan to Eliminate Drunk Driving
Thirty years after a grieving mother started the movement to stop drunk driving, and a decade since the successful passage of the lifesaving national .08 BAC limit, hundreds of victims and activists from across the country today rallied at the nation's Capitol to mark Mothers Against Drunk Driving's (MADD) 30th Anniversary and to unveil its MADD 3.0 Action Plan, calling on Congress to pass legislation to eliminate drunk driving in America.
http://www.prnewswire.com/news-releases/madd-marks-30th-anniversary-with-capitol-hill-rally-unveiling-tech-based-madd-30-action-plan-to-eliminate-drunk-driving-103620734.html

BBC News (UK) - Fresh call for alcohol glass ban
Alcohol should be served far more often in plastic glasses and bottles to reduce the injury toll from violent attacks, says a researcher.
http://www.bbc.co.uk/news/health-11392685

Herald Scotland (Scotland) - Police chief challenges minimum drink price opponents
The chief constable of the country’s biggest police force has issued a challenge to those who voted down minimum alcohol pricing this week to come up with an alternative.
http://www.heraldscotland.com/news/home-news/police-chief-challenges-minimum-drink-price-opponents-1.1057451

Radio New Zealand (New Zealand) - Cabinet rejects advice on lowering alcohol limit
The Government made a mistake when it rejected hundreds of pages of official advice encouraging it to lower the adult blood alcohol level, health lobby groups say.
http://www.radionz.co.nz/news/national/57429/cabinet-rejects-advice-on-lowering-alcohol-limit

UK Net Guide (Scotland) - Minimum alcohol price plans defeated by MSPs
MSPs have rejected the Scottish government's proposal to introduce a minimum price for alcohol.
http://www.uknetguide.co.uk/Latest-News/Minimum-alcohol-price-plans-defeated-by-MSPs-800078853.html




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Press Release - SMART Recovery Announces 600th Meeting

SMART Recovery announces its 600th meeting as it continues expanding face-to-face group meetings nationally and internationally. SMART Recovery, the leading self-empowering addiction recovery support group, offers tools for overcoming addiction based on the latest scientific research and is now doing so in more and more cities and towns.    > > > >

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Nalmefene for treatment of alcohol dependence

 

Alcohol use and dependence are frequent disorders. Despite numerous established psychosocial approaches, relapse to heavy drinking is common in alcohol-dependent patients after detoxification and relapse prevention remains a significant medical challenge.

The opioidergic system plays a crucial role in mediating the rewarding effects of alcohol, in part by modulating dopaminergic neurotransmission in mesolimbic brain areas.

This review will discuss the neurochemical basis of alcoholism with respect to the opiodergic system. Nalmefene is an alternate opioid receptor that also targets the kappa opioid receptors and thus offers a different treatment approach. The treatment studies conducted so far are discussed.

We present a comprehensive overview of the implication of the opioidergic system in mediating the rewarding effects of alcoholism and the preclinical and clinical studies conducted so far with nalmefene.

Although the number of clinical studies conducted with naltrexone by far exceeds the number conducted with nalmefene, the four studies on nalmefene published so far may indicate a role of this opioid antagonist in the treatment of alcoholism.

Results of some ongoing studies on nalmefene will provide additional data on its use for this indication.

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Request Reprint E-Mail: Susanne.Roesner@med.uni-muenchen.de   

NIAAA Director's Report on Institute Activities to the 125th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism - September 23, 2010

Contents

A.  Legislation, Budget, and Policy	F. News Media Interactions
B. Director's Activities	G. NIAAA Staff and Organization
C. Staff Honors	H. What's Ahead
D. Press Releases	I. NIAAA Program Annoucement and Request for Applications Information
E. Multi-Media Products	J. NIAAA Research Programs

Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers

N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers.

This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers.

A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects.

Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans.

The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls.

There was no relationship between immunoblot reactivity and consumption of any specific type of wine.

No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine.

In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins.

Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. 

The clinical significance of these findings remains to be elucidated.

 
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Request Reprint E-Mail:  arturo.gonzalez.quintela@usc.es 

Temporal and spatial patterns in the rate of alcohol withdrawal syndrome in a defined community

There is a paucity of data about the epidemiology of alcohol withdrawal syndrome (AWS) and, particularly, with regard to temporal trends and sociodemographic factors.

This study included 7,195 episodes of AWS in a defined community (Galicia, Spain) over a 11-year period. We looked for geographical correlations between AWS rate and sociodemographic factors (education and socioeconomic levels and rates of occupational activity and unemployment) within respective districts. We also investigated the inter- and intra-annual time trends for AWS.

The median age of the participants was 49 years (interquartile range, 41–60 years), and 85% were men. 

The annual frequency of AWS episodes remained stable during the study period, with a consistent peak in episodes during the summer months and lowest frequency of episodes in winter months.

The age- and sex-adjusted geographical distribution of the AWS rate was uneven; districts with high rate tended to cluster.

The mean education level was negatively correlated with AWS rate within a given district after adjusting for socioeconomic level, occupational activity rate, and unemployment rate.

In conclusion, we identified characteristic temporospatial patterns of AWS rate in this defined community. The rate of AWS tended to be higher in the summer months and lower in the winter months. The rate of AWS was higher in districts with low education levels.

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Request Reprint E-Mail: arturo.gonzalez.quintela@usc.es  

Overexpression of 5-HT1B mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption

Serotonin 1B (5-HT1B) heteroreceptors on nucleus accumbens shell (NAcSh) projection neurons have been shown to enhance the voluntary consumption of alcohol by rats, presumably by modulating the activity of the mesolimbic reward pathway.

The present study examined whether increasing 5-HT1B receptors expressed on NAcSh projection neurons by means of virus-mediated gene transfer enhances ethanol consumption during the initiation or maintenance phase of drinking and alters the temporal pattern of drinking behavior.

Animals received stereotaxic injections of viral vectors expressing either 5-HT1B receptor and green fluorescent protein (GFP) or GFP alone. Home cages equipped with a three-bottle (water and 6 and 12% ethanol) lickometer system recorded animals’ drinking behaviors continuously, capturing either initiation or maintenance of drinking behavior patterns.

Overexpression of 5-HT1B receptors during initiation increased consumption of 12% ethanol during both forced-access and free-choice consumption. There was a shift in drinking pattern for 6% ethanol with an increase in number of drinking bouts per day, although the total number of drinking bouts for 12% ethanol was not different.

Finally, increased 5-HT1B1B receptors facilitate longer drinking bouts of more modest volumes.

Taken together, these results indicate that 5-HT1B receptors expressed on NAcSh projection neurons facilitate ethanol drinking, with different effects during initiation and maintenance of ethanol-drinking behavior.

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Request Reprint E-Mail:  amyfuray@uw.edu    

Assessment of GABA-B, metabotropic glutamate, and opioid receptor involvement in an animal model of binge drinking

Drinking to intoxication or binge drinking is a hallmark characteristic of alcohol abuse. Although hard to model in rodents, the scheduled high alcohol consumption (SHAC) procedure generates high, stable ethanol intake and blood ethanol concentrations in mice to levels consistent with definitions of binge drinking.

The purpose of the present studies was to determine the effects of pharmacological manipulation of the opioidergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic systems on binge drinking with the SHAC procedure.

Parallel manipulations were conducted in mice trained in operant self-administration of either sucrose or ethanol. For the SHAC procedure, genetically heterogeneous Withdrawal Seizure Control mice were given varying periods of fluid access, with a 30-min ethanol session every third day (total of seven).

Mice were pretreated intraperitoneally with naltrexone (0, 0.6, or 1.25mg/kg), baclofen (0, 2.5, or 5.0mg/kg), or 2-methyl-6-(phenylethynyl)-pyridine (MPEP; 0, 3.0, or 10.0mg/kg) before each ethanol session. 

For the operant self-administration procedure, separate groups of C57BL/6 mice were trained to complete a single response requirement (16 presses on the active lever) to gain 30min of access to an ethanol or a sucrose solution. Mice received pretreatments of the same doses of naltrexone, MPEP, or baclofen before the self-administration sessions, with saline injections on intervening days.

Naltrexone produced a dose-dependent decrease in binge drinking, and the highest dose also significantly decreased operant self-administration of ethanol and sucrose.

Both doses of baclofen significantly decreased binge alcohol consumption, but the higher dose also tended to decrease water intake. The highest dose of baclofen also significantly decreased operant self-administration of sucrose. MPEP (10mg/kg) significantly decreased binge alcohol consumption and sucrose self-administration

These results indicate that manipulation of the opioidergic, glutamatergic, and GABAergic systems significantly decreased binge drinking.

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Request Reprint E-Mail:   tanchuck@ohsu.edu

 

Ethanol-induced downregulation of the angiotensin AT2 receptor in murine fibroblasts is mediated by PARP-1

Molecular mechanisms accompanying ethanol-induced cytotoxicity remain to be defined.

The renin–angiotensin system with its respective receptors, the angiotensin AT1 and AT2 receptor (AT1R and AT2R), has been implicated in these processes. The AT2R seems to counteract the pro-inflammatory, pro-hypertrophic, and pro-fibrotic actions of the AT1R and is involved in cellular differentiation and tissue repair.

Recently, we identified poly(ADP-ribose) polymerase-1 (PARP-1) as a novel negative transcriptional regulator of the AT2R.  However, the complex interactions between ethanol, PARP-1, and the AT2R are largely unknown.

In this in vitro study, we aimed to clarify whether acute ethanol treatment modifies AT2R promoter activity or AT2R mRNA and protein levels and whether PARP-1 is involved in ethanol-mediated regulation of the AT2R.

Murine fibroblasts of the R3T3 and MEF line (murine embryonic fibroblasts) were exposed to ethanol for 24h. AT2R promoter activity, mRNA and protein levels were analyzed with and without PARP-1 inhibition and in PARP-1 knockout MEF cells. Expression of PARP-1 was analyzed over course of time, and cell viability and DNA fragmentation were measured on single-cell level by flow cytometry.

Ethanol exposition induced substantial downregulation of the AT2R on promoter, mRNA and protein levels in a dose-dependent manner. Pharmacological inhibition or ablation of PARP-1 completely abolished this effect.

Ethanol treatment did not have any effect on AT1R mRNA and protein levels in MEF cells.

Further, acute ethanol treatment promoted DNA fragmentation and caused transcriptional induction of PARP-1.

Our findings reveal that PARP-1 is an upstream transcriptional regulator of the AT2 receptor in the context of ethanol exposure and represses the AT2R gene in fibroblasts in vitro.

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Request Reprint E-Mail:  mario.menk@charite.de

Variations in expression of the potentially tissue-protective AT2R might contribute to ethanol-mediated pathology.

Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains

Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced.

To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions.

Adult male Wistar rats were subjected to intermittent ethanol vapor (14h on/10h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8–12h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time.

The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period.

NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time.

Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain.

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Request Reprint E-Mail:   b_walker@wsu.edu

Fine mapping and expression of candidate genes within the chromosome 10 QTL region of the high and low alcohol-drinking rats

The high and low alcohol-drinking (HAD and LAD) rats were selectively bred for differences in alcohol intake.

The HAD/LAD rats originated from the N/Nih heterogeneous stock developed from intercrossing eight inbred rat strains.

The HAD×LAD F2 were genotyped, and a powerful analytical approach, using ancestral recombination and F2 recombination, was used to narrow a quantitative trait loci (QTL) for alcohol drinking to a 2-cM region on distal chromosome 10 that was in common in the HAD1/LAD1 and HAD2/LAD2 analyses.

Quantitative real-time PCR was used to examine mRNA expression of six candidate genes (Crebbp, Trap1, Gnptg, Clcn7, Fahd1, and Mapk8ip3) located within the narrowed QTL region in the HAD1/LAD1 rats.

Expression was examined in five brain regions, including the nucleus accumbens, amygdala, caudate putamen, hippocampus, and prefrontal cortex.

All six genes showed differential expression in at least one brain region.

Of the genes tested in this study, Crebbp and Mapk8ip3 may be the most promising candidates with regard to alcohol drinking.

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Generation alcohol: is drinking damaging childhood? 2 November 2010, London

The trend for drinking at home has risen sharply in recent years. What does this mean for parents and their children? Youth drinking and the generational impact of parental drinking are two ongoing issues of concern to treatment providers, politicians and the public. Alcohol Concern’s flagship event of the year will hear from academics, experts and politicians on what needs to be done to protect children from alcohol harm.

Event:

Generation alcohol: Is drinking damaging childhood?

Start Date:

Tuesday 02 November 2010

Start Time:

10.00am (9.30am for AGM)

End Time:

4.45pm

Location:

London

Conference  Webpage

Future for alcohol policy? DDN article September 2010

This month's Drink & Drugs News (DDN) features an article exploring the future for alcohol policy given the significant changes facing the field. The comment explores the possible threats and opportunities for alcohol as it seeks to find its voice within wider substance misuse and public health agendas.   > > > >

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KBS 2011 - 37th Annual Alcohol Epidemiology Symposium of the Kettil Bruun Society

The principal aims of the KBS are to instigate further social, epidemiological, and cross-cultural research on alcohol use, to promote the exchange of scientific knowledge and experiences among researchers from various disciplines and to encourage international collaboration. The comparison of social and epidemiological developments found in different countries makes it possible to disentangle major trends from underlying patterns of alcohol use. This is particularly useful for the development of effective strategies to regulate alcohol use - an aspect which is of great interest in many countries.

The primary purpose of the symposium is to provide a forum where researchers involved in studies on alcohol can exchange ideas about their ongoing research. The scope of the symposium includes studies of determinants and consequences of drinking, drinking practices, attitudes and the social and institutional responses to drinking related harms. Empirical research, theoretical papers and reviews of the literature are welcome. Epidemiology is broadly construed and includes research in a variety of disciplines, such as psychology, sociology, criminology, economics, history and other disciplines.

Conference Webpage

Age Differences in Long-Term Patterns of Change in Alcohol Consumption Among Aging Adults

To estimate patterns of long-term, within-person, changes in alcohol consumption among adults of different ages and assess key predictors of alcohol-use patterns over time.

 

Data came from 3,617 adults, interviewed up to four times between 1986 and 2002. Multilevel multinomial logit models estimated the odds of abstinence and heavy drinking relative to moderate drinking.

 

The odds of abstinence increased and the odds of heavy drinking decreased during the study period. Older adults experienced faster increases in abstinence than younger adults. However, data extrapolations suggest that current younger adults are more likely to be abstinent and less likely to be heavy drinkers during late life than current older adults. Time-varying health, social, and lifestyle factors account for some of these patterns.

 

Drinking behavior in our aging population appears to be on a relatively promising course, perhaps reflecting the effectiveness of public health efforts. 


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