Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H₂[¹⁵O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction.

Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated.

These findings suggest that DBS of the NAcc may act partially by improving behavioral control.


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Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear.

In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation.

We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47^phox and p67^phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47^phox and p67^phox, which were prerequisites for NOX assembly and activation.

Knocking down p47^phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation.

Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation.

These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons.

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The Economic Gains of Achieving Reduced Alcohol Consumption Targets for Australia

To inform prevention policy, we estimated the economic benefits to health, production, and leisure in the 2008 Australian population of a realistic target reduction in per capita annual adult alcohol consumption.

We chose a target of 6.4 liters annually per capita on average. We modeled lifetime health benefits as fewer incident cases of alcohol-related disease, deaths, and disability adjusted life years. We estimated production gains with surveyed participation and absenteeism rates. We valued gains with friction cost and human capital methods. We estimated and valued household production and leisure gains from time-use surveys.

A reduction of 3.4 liters of alcohol consumed annually per capita would result in one third fewer incident cases of disease (98 000), deaths (380), working days lost (5 million), days of home-based production lost (54 000), and a A$ 789-million health sector cost reduction. Workforce production had a A$ 427 million gain when we used the friction cost method. By contrast, we estimated a loss of 28 000 leisure days and 1000 additional early retirements.

Economic savings and health benefits from reduced alcohol consumption may be substantial—particularly in the health sector with reduced alcohol-related disease and injury.

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Request Reprint E-Mail: anne.magnus@deakin.edu.au

Histamine H3 receptor: a novel therapeutic target in alcohol dependence?

The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas.

Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference.

Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.


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Amygdala 14-3-3ζ as a Novel Modulator of Escalating Alcohol Intake in Mice

Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood.

We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice.

Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake.

Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake.

Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol.

This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use.


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ANNOUNCEMENT AND CALL FOR ABSTRACTS

The African Centre for Research and Information on Substance Abuse (CRISA) announces the Tenth in a series of highly regarded biennial international conference on drugs in Africa scheduled to take place in Abuja, Nigeria, in July 2012.

The organizers invite you to this very important conference, which will focus attention on the social and cultural determinants of substance use and abuse in different African societies.

Interested researchers in various academic disciplines, policy experts, practitioners, activists, and students are encouraged to submit abstracts of papers for presentation at the conference.

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Alcohol and drug problems would be categorized differently in revised manual

What’s in a name? That’s a question that experts are wrestling with as they prepare to revise the diagnostic manual that spells out the criteria for addiction and other substance-use problems.

The catalyst for this discussion is a set of proposed changes to the Diagnostic and Statistical Mual of Mental Disorders, the reference guide upon which clinicians, researchers, insurers and others rely to identify and classify psychiatric disorders. The revised guide, called DSM-5, will incorporate changes to more than a dozen categories of disorders, including those related to mood, eating and personality, as well as substance use and addiction. > > > > Read More

Alcohol News - 22/2012

ERR News (Estonia) - Poll: 75% Say Estonians Drink Too Much, 2% Admit It

In a recently published survey by the Institute of Economic Research, 75 percent of respondents said Estonians drink too much alcohol.

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Helsinki Times (Finland) - Debate on alcohol advertising ban rages on

THE debate on the draft bill to restrict alcohol advertising, put forward by Minister of Health and Social Services Maria Guzenina-Richardson (SDP), is heating up with sports bodies, media groups and industry federations all weighing in on the discussion.

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Scotland Courier (Scotland) - Minimum alcohol pricing plans cleared in Parliament

Scots could face the highest alcohol prices in the UK as early as next April after MSPs approved legislation to crack down on problem drinkers.

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Fox News (USA) - Study: Nearly a quarter of US suicide victims intoxicated at time of death

A large-scale study has found that nearly a quarter of U.S. suicide victims are legally intoxicated when they die. These victims are also much more likely than their sober counterparts to commit suicide by violent means such as using a firearm, hanging themselves or falling to their deaths.

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Stock and Land (Australia) - Alcohol warning labels shunned by industry despite research

THE alcohol industry is putting ''booze before babies'' by making false and misleading claims to a parliamentary inquiry into fetal alcohol disorders, a publicly-funded research body says.

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Canada.com (Canada) - Health Canada slow to move against alcoholic energy drinks

Health Canada isn't ready to crack down on pre-mixed alcoholic energy drinks, despite a long-standing request from government inspectors for direction on what "action can be taken against these products," internal records show.

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The Independent (Scotland) - Scottish Government set to lower drink-drive limit

The Scottish Government have today announced plans to almost half the drink-drive limit with a new scheme being implemented “as soon as possible”.

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Bloomberg (Russia) - Yakutia Restricted Alcohol Retail Sale Till Lunch Time, RIA Says

Authorities of the Republic of Yakutia, part of which lies in Russia’s Arctic zone, banned sales of spirits in stores from 8 p.m. till 2 p.m. to combat alcohol addiction, RIA Novosti said.

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Zee News (India) - Soon alcohol content in alcoholic beverages to be regulated

For the first time, India`s food regulator FSSAI has finalised draft standards for all categories of alcoholic beverages like wine, beer, whisky, rum, gin and vodka to set the maximum permissible limits of alcohol in these drinks and thus, mandate safety standards.

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TVNZ (New Zealand) - Hike alcohol price to target binge-drinking: Doctor

A Wellington doctor who is "sick" of dealing with drunk patients says raising the price of alcohol is the best way to combat New Zealand's binge-drinking culture.

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The Independent Florida Alligator (USA) - Diagnostic manual re-classifies alcohol abuse

Nearly 40 percent of college students at four-year U.S. institutions could be deemed alcoholics next year, according to the label in the newest edition of the Diagnostic and Statistical Manual of Mental Disorders.

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The Hindu (India) - Ban sale of tobacco, alcohol: expert

Noted cardiologist G.K. Sinha on Sunday said it was high time to impose a ban on tobacco and alcohol to prevent life-threatening diseases claiming a heavy toll.

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Mirror.co.uk (UK) - Booze shock: Alcohol puts a child under FIVE in hospital every week

The NHS says it is growing trend as every week three 10 and 11-year-olds are taken to hospital in England after drinking too much.

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Business Review Europe - Improving Accuracy in Roadside Breath Testing Use Breathalyzer Equalizer

Police officers use a variety of field sobriety tests to evaluate a driver's level of impairment. When making an arrest decision, officers rely heavily on the roadside handheld breathalyzer or PBT (Preliminary Breath Test) because it provides a direct digital reading of approximate blood alcohol level.

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The Independent (UK) - Deep concerns over government plans to cut benefits for alcoholics and drug addicts who refuse treatment

Doctors and addiction charities today expressed deep concerns over government plans to cut the benefits of people suffering from alcoholism or drug addiction who refuse treatment.

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China Daily (China) - Drunken driving law not consistently applied

Legal experts suggested that the Supreme People's Court should make a judicial interpretation to standardize the penalties for drunken driving, Beijing News reported.

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New Zealand Herald (New Zealand) - Drinking big concern in community, says survey

Auckland communities are becoming more aware of problems caused by alcohol, two out of three people surveyed saying liquor has a negative effect on life in the city.

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M.A.D (Mongolia) - MONGOLIA’S DROWNING FUTURE

Various punishment measures were taken on drunkards. In the 13th century, the Ikh Zasag Law of the Great Mongol Empire stated “If a person arrives drunk at a workplace, the first time impose a fine of a weapon he is carrying with him, second time impose the fine of a horse he is riding, third time cut off an extremity of the body. If a fourth time occurs, expel him out of the territory.”

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Telegraph.co.uk (France) - Bordeaux hit by spate of binge drinking drownings

France's wine capital Bordeaux has been struck by spate of binge drinking drownings in its river Garonne, with five young men dying in the past ten months.

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Indicators for elevated risk factors for alcohol-withdrawal seizures: an analysis using a random forest algorithm

Alcohol-withdrawal seizures (AWS) are an important and relevant complication during detoxification in alcohol-dependent patients. Therefore, it is important to evaluate the individual risk for AWS. We apply a random forest algorithm to assess possible predictive markers in a large sample of 200 alcohol-dependent patients undergoing alcohol withdrawal. This analysis showed that the combination of homocysteine, prolactin, blood alcohol concentration on admission, number of preceding withdrawals, age and the number of cigarettes smoked may successfully predict AWS.

In conclusion, the results of this analysis allow for origination of further research, which should include additional biological and psychosocial parameters as well as consumption behaviour.


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Request Reprint E-Mail: hillemacher.thomas@mh-hannover.de

Blockade of the brain histamine H3 receptor by JNJ-39220675: preclinical PET studies with [11C] GSK189254 in anesthetized baboon

The preclinical characterization of a series of aryloxypyridine amides has identified JNJ-39220675 ((4- cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone) as a high-affinity histamine H3 receptor antagonist and a candidate for further drug development
particularly in the treatment of alcohol-related behaviors.

This study measured brain histamine H3 receptor
blockade by JNJ-39220675 (1 mg/kg) in the female baboon.

Positron emission tomography imaging and [11C]
GSK189254, a reversible high-affinity radiotracer with specificity for the histamine H3 receptor, was used to measure histamine H3 receptor availability at baseline and after i.v. and oral administration of JNJ-39220675 (1 mg/kg) in
the anesthetized baboon. Histamine H3 receptor availability was estimated as the total distribution volume (VT) in brain regions. The sensitivity of [11C]GSK189254 binding to injected mass and carryover effects was determined.

JNJ-39220675 produces robust (ca. 90 %) blockade of [11C]GSK189254 binding after i.v. and oral administration. After oral administration of JNJ-39220675 (1 mg/kg), the fractional receptor occupancy was >0.9 at 90 min with a
slight increase from 90 to 240 min. Similar to prior studies in humans, VT was highly sensitive to the mass of GSK189254 with ED50 estimated to be 0.16 μg/kg.

The robust blockade of binding of [11C] GSK189254 by JNJ-39220675 demonstrates that this compound readily penetrates the blood–brain barrier and occupies the histamine H3 receptor after oral administration at low plasma concentrations (∼1 ng/cc) supporting further
drug development for alcohol addiction and other disorders.

This study corroborates prior reports of the high sensitivity of [11C]GSK189254 to injected mass at doses >0.1 μg/kg.


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A systematic review of psychological interventions for excessive alcohol consumption among people with psychotic disorders

Excessive alcohol consumption is common among people with psychotic disorders. While there is an extensive literature on the efficacy of psychological treatments for excessive drinking, few studies have examined interventions addressing this issue among people with psychotic disorders.

Systematic searches in PubMed and PsycINFO were conducted to identify randomized controlled trials comparing manual-guided psychological interventions for excessive alcohol consumption among individuals with psychotic disorders. Of the 429 articles identified, seven met inclusion criteria. Data were extracted from each study regarding study sample characteristics, design, results, clinical significance of alcohol consumption results, and methodological limitations.

Assessment interviews, brief motivational interventions, and lengthier cognitive behavior therapy have been associated with reductions in alcohol consumption among people with psychosis. While brief interventions (i.e. 1–2 sessions) were generally as effective as longer duration psychological interventions (i.e. 10 sessions) for reducing alcohol consumption, longer interventions provided additional benefits for depression, functioning, and other alcohol outcomes.

Excessive alcohol consumption among people with psychotic disorders is responsive to psychological interventions. It is imperative that such approaches are integrated within standard care for people with psychosis.

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Request Reprint E-Mail: amanda.baker@newcastle.edu.au

Alcohol-use disorders: physical complications Evidence Update March 2012

The latest evidence update from NHS Evidence Alcohol-use Disorders: Physical Complications is a summary of selected new evidence relevant to NICE clinical guideline 100 Diagnosis and Management of Alcohol-related Physical Complications (2010).


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Prevalence of ethanol and illicit drugs in road traffic accidents in the centre of Portugal: An eighteen-year update

This study presents the prevalence of ethanol and illicit drugs in fatal road traffic accident victims in the Centre of Portugal between January 1990 and December 2007.

Among the violent deaths, road traffic accidents presented the highest percentage (around 35%; n=3095), but decreasing throughout the years. Accidents were preponderant in males (about 80%; n=2402), between 21 and 30 years-old. Accidents involving drivers (55%; n=1310) were of the most common, being the car the main vehicle (45%), followed by the motorcycle (40%).

An alcohol analysis request was present in 50% of the cases (n=1687), but increasing each year. Ethanol concentrations >1.2g/L, the legal limit in Portugal, were found in 55% (n=283) of the cases.

Concerning drugs of abuse requests, only 4.4% (n=137) and 17.3% (58 cases) of the cases included the analysis at the Forensic Pathology Department (FPD) and at the Medico-Legal Office (MLO), respectively. Among the road accident cases analysed, 18 were positive, mainly in men (84%), between 21 and 30 years-old; opiates (47.1%; n=8) and cannabinoids (50%; n=4) were the most found, at the FPD and at the MLO, respectively.

In conclusion, ethanol was identified as a key factor to traffic accidents, which explains the definition of specific legislation and methods of enforcement to prohibit this form of impairing. Nevertheless, ethanol still remains the psychoactive substance most frequently identified in the blood of divers killed in road-traffic crashes, recommending additional actions of supervision and control.

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Request Reprint E-Mail: helenateixeira@dcinml.mj.pt

Requirement of central ghrelin signaling for alcohol reward

The stomach-derived hormone ghrelin interacts with key CNS circuits regulating energy balance and body weight. Here we provide evidence that the central ghrelin signaling system is required for alcohol reward.

Central ghrelin administration (to brain ventricles or to tegmental areas involved in reward) increased alcohol intake in a 2-bottle (alcohol/water) free choice limited access paradigm in mice.

By contrast, central or peripheral administration of ghrelin receptor (GHS-R1A) antagonists suppressed alcohol intake in this model.

Alcohol-induced locomotor stimulation, accumbal dopamine release and conditioned place preference were abolished in models of suppressed central ghrelin signaling: GHS-R1A knockout mice and mice treated with 2 different GHS-R1A antagonists.

Thus, central ghrelin signaling, via GHS-R1A, not only stimulates the reward system, but is also required for stimulation of that system by alcohol.

Our data suggest that central ghrelin signaling constitutes a potential target for treatment of alcohol-related disorders.


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A Cultural and Social Cognitive Model of Differences in Acculturation Orientations, Alcohol Expectancies, and Alcohol-Related Risk Behaviors Among His

The present study used a cultural and social cognitive conceptual framework to investigate whether alcohol expectancies and valuations would mediate the associations between specific acculturation orientations and alcohol-related risk behaviors.

The sample comprised 1,527 Hispanic students attending colleges and universities in diverse regions of the United States. Respondents completed self-report measures of Hispanic and American cultural practices; alcohol expectancies and valuations; and self-reported frequency of hazardous alcohol use, binge drinking, sexual activity under the influence of alcohol, driving under the influence of alcohol, and riding with a drunk driver. Latent class analysis was used to classify participants into acculturation orientations.

Results indicated that acculturation orientations were differentially associated with alcohol-related risk outcomes, with separated bicultural and low bicultural orientations inversely related to all of the alcohol-related risk behaviors except for riding with a drunk driver. Negative expectancy valuations were positively associated with endorsement of binge drinking and drunk driving and negative expectancies were negatively associated with binge drinking, drunk driving, and riding with a drunk driver. With the exception of sexual activity under the influence of alcohol, the associations between acculturation orientations and alcohol-related risk behaviors were partially mediated by positive alcohol expectancies.

Our findings provided relevant data that are informative for preventing alcohol and related risk behaviors among Hispanic college students.

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

Substance Misuse, October-December 2011

Statistics on Substance Misuse in Wales include data concerning people presenting to treatment services for substance misuse. The latest release updates the statistics previously released on 29 February 2012.

The key points from the latest release are:

• There were more than 6,800 referrals for treatment of alcohol or drug misuse notified to the database. During the quarter over 4,100 assessments were carried out by treatment services and over 3,300 treatments commenced.
• 51 per cent (3,500) of referrals related to misuse of alcohol, 41 per cent (2,800) related to misuse of drugs and 8 per cent (500) of referrals had no main substance reported.
• Of those where a main substance was reported 56 per cent of referrals were for alcohol and 44 per cent for drugs misuse. Heroin accounted for 46 per cent of all referrals for which drugs were specified as the main substance, with cannabis (17 per cent) and cocaine (10 per cent) the next most common drugs.
• Males accounted for the majority of all referrals for both alcohol (64 per cent) and drugs (75 per cent).
• 71 per cent of referrals for any substance were assessed within 10 working days of referral and 91 per cent of people were given treatment within 10 working days of assessment.

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Global Actions May 24, 2012

Key Recent Milestones:

· Colombia: Global Actions has been invited to participate as a key stakeholder in Colombia’s “Mesa por la Vida: Recuperación Integral de la Zona Rosa.” The project focuses on improving the safety of Bogota’s nightlife by promoting moderate alcohol consumption and working to reduce underage drinking, public drinking, drink driving, and noncommercial alcohol consumption.


Global Actions in Focus: Vietnam

Global Actions Vietnam held its first Noncommercial Alcohol workshop in April 2012 in Hanoi, “Production, Consumption, and Use of Noncommercial Alcohol in Vietnam.”

Co-sponsored by the Vietnam Beer Alcohol Beverage Association (VBA), the event featured a discussion of the state of unrecorded alcohol in Vietnam and remarks from experts in the research field, including VBA Chairman Dr. Nguyen Van Viet.

Institute for Population and Social Studies (IPSS) Vice Director Dr. Luu Bich spoke on findings from National Economic University (NEU) and ICAP’s 2011 qualitative survey in Bac Ninh, Quang Binh, and Tien Giang provinces. ICAP’s Brett Bivans remarked on the noncommercial alcohol issue globally, highlighting the need for continuing assessment and solutions.

In addition to the successful noncommercial alcohol workshop, Global Actions continues to see steady progress in the drink driving initiative.

“The Da Nang project team has well applied the combination of education and enforcement activities with the knowledge gained from our capacity-building workshops,” said Global Actions Country Manager Lan Huong Nguyen.


In April 2012, Global Actions worked with the Da Nang Traffic Police Department to implement the most recent drink driving education campaign. We also worked with the Traffic Safety Committee to produce leaflets, panels, and a manual of traffic safety named “Prevention of Harmful Drinking While Driving” that will be distributed to the Da Nang public.

What’s Happening Next:

· Mexico: ICAP’s Brett Bivans is speaking on the topic of responsible marketing of beverage alcohol through compliance monitoring at the CONAR-CIVyL Signing Ceremony on May 24. ICAP is also set to launch the Global Actions campaign “Towards zero drink- driving deaths in Puebla” on May 30.

Caffeinated alcoholic beverages: report, policy recommendations and fact sheets

A new report from the Canadian Centre on Substance Abuse (CCSA) and the Centre for Addictions Research of British Columbia (CARBC) examines the trends and risks of alcohol and caffeine consumption, and provides targeted recommendations for policy makers, public health organizations, healthcare providers and researchers.

View the recommendations in the full report, Caffeinated Alcoholic Beverages in Canada: Prevalence of Use, Risks and Recommended Policy Responses.

Read the accompanying Policy Brief on Alcohol and Caffeine.

CCSA and CARBC have also developed alcohol and caffeine fact sheets for parents and youth:

Youth – Alcohol and Caffeine: a Bad Buzz
Parents – Alcohol and Caffeine: a Bad Buzz

Does Staying in school (AND NOT WORKING) Prevent Teen Smoking and Drinking?

Previous work suggests but cannot prove that education improves health behaviors. We exploit a randomized intervention that increased schooling (and reduced working) among male students in the Dominican Republic, by providing information on the returns to schooling.

We find that treated youths were much less likely to smoke at age 18 and had delayed onset of daily or regular drinking. The effects appear to be due to changes in peer networks and disposable income.

We find no evidence of a direct impact of schooling on rates of time preference, attitudes towards risk or perceptions that drinking or smoking are harmful to health, though our measures of these factors are more limited.


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Request Reprint E-Mail: robertjensen@ucla.edu

Scotland passes minimum pricing bill; Irish health minister announces ban on alcohol sports sponsorship

The Scottish Government has passed the Alcohol Minimum Pricing Bill, meaning a 50 pence minimum unit price (MUP) could be in place north of the border by April next year. The Bill requires Royal Assent and still faces the threat of potential legal challenges as warned of by sections of the alcohol industry.

A 50 pence MUP would set a minimum floor price for an average strength bottle of wine at £4.69, vodka at £13.13 a bottle (70cl) and a standard four-pack of lager would need to cost at least £3.52. The Bill sets a minimum price for a unit of alcohol as a condition of licence.

However most drinks would be unaffected, especially those sold in pubs and restaurants. The minimum price would not be raised for at least two years and is reported to include a "sunset clause". The move is expected to save lives and reduce crime based on evidence linking price and consumption and modelling work by the University of Sheffield. > > > > Read More