ALCOHOL REPORTS

Wednesday, December 26, 2012

Actual and Perceived Units of Alcohol in a Self-Defined “Usual Glass” of Alcoholic Drinks in England

Several studies have found participants pour more than 1 standard drink or unit as their usual glass. This is the first study to measure actual and perceived amounts of alcohol in a self-defined usual glass of wines and spirits in the general population.

Participants were a convenience sample of adults who drink alcohol or who pour drinks for other people (n = 283, 54% women) at 6 sites in South East England. The survey was face to face and comprised a self-completion questionnaire and pouring task. Estimation accuracy, categorised as correct (±0.5 units), underestimate (>0.5 units), or overestimate (>0.5 units) was the main outcome.

The mean number of units poured was 1.90 (SD 0.80; n = 264) for wine and 1.93 (SD 0.78; n = 201) for spirits. The amount of alcohol in a self-defined usual glass was estimated in 440 glasses (248 wine and 192 spirits). Overestimation took place in 42% glasses of spirit poured and 29% glasses of wine poured, and underestimation in 17 and 19%, respectively. Multinomial logistic regression found volume poured to be significantly associated with underestimating both wines and spirits, and additionally for wine only, belonging to a non-white ethnic group and being unemployed or retired. Not having a university degree was significantly associated with overestimating both drink types.

This study is the first in the general population and did not identify systematic underestimation of the amount of alcohol in a self-defined usual glass. Underestimation is significantly associated with volume poured for both drink types; therefore, advocating pouring smaller glasses could reduce underestimation of alcohol consumption.

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Request Reprint E-Mail: s.boniface@ucl.ac.uk

Local Changes in Neurosteroid Levels in the Substantia Nigra Reticulata and the Ventral Tegmental Area Alter Chronic Ethanol Withdrawal Severity in Male Withdrawal Seizure-Prone Mice

Allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acid_A receptors (GABA_ARs) that affects ethanol (EtOH) withdrawal. Finasteride (FIN), a 5α-reductase inhibitor that blocks the formation of ALLO and other GABAergic neurosteroids, alters EtOH sensitivity. Recently, we found that Withdrawal Seizure-Prone mice from the first genetic replicate (WSP-1) exhibited behavioral tolerance to the anticonvulsant effect of intrahippocampal ALLO during EtOH withdrawal and that intrahippocampal FIN significantly increased EtOH withdrawal severity. The purpose of this study was to determine whether neurosteroid manipulations in the substantia nigra reticulata (SNR) and ventral tegmental area (VTA) produced effects during EtOH withdrawal comparable to those seen with intrahippocampal ALLO and FIN.

Male WSP-1 mice were surgically implanted with bilateral guide cannulae aimed at the SNR or VTA at 2 weeks prior to EtOH vapor or air exposure for 72 hours. Initial studies examined the anticonvulsant effect of a single ALLO infusion (0, 100, or 400 ng/side) at a time corresponding to peak withdrawal in the air- and EtOH-exposed mice. Separate studies examined the effect of 4 FIN infusions (0 or 10 μg/side/d) during the development of physical dependence on the expression of EtOH withdrawal.

ALLO infusion exerted a potent anticonvulsant effect in EtOH-naïve mice, but a diminished anticonvulsant effect during EtOH withdrawal. Administration of FIN into the SNR exerted a delayed proconvulsant effect in EtOH-naïve mice, whereas infusion into the VTA increased EtOH withdrawal duration.

Activation of local GABA_ARs in the SNR and VTA via ALLO infusion is sufficient to exert an anticonvulsant effect in naïve mice and to produce behavioral tolerance to the anticonvulsant effect of ALLO infusion during EtOH withdrawal. Thus, EtOH withdrawal reduced sensitivity of GABA_ARs to GABAergic neurosteroids in 2 neuroanatomical substrates within the basal ganglia in WSP-1 male mice.

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Request Reprint E-Mail: tanchuck@ohsu.edu

Motives to Drink or Not to Drink: Longitudinal Relations Among Personality, Motives, and Alcohol Use Across Adolescence and Early Adulthood

Adolescent selective intervention programs for alcohol have focused on the identification of youth at risk as a function of personality and associated alcohol-related cognitions. Research into the role of personality, drinking motivations, and alcohol-related outcomes has generally focused exclusively on motives to drink. We expand on this literature by focusing on both motives to drink and motives not to drink across time from adolescence to early adulthood in a community sample.

Using 3 waves of data from 3 cohorts from the Rutgers Health and Human Development Project (n = 1,380; 49.4% women), we modeled the influence of baseline alcohol consumption, disinhibition (DIS), and harm avoidance (ages 15, 18, and 21 years) on drinking motives and motives not to drink 3 years later (ages 18, 21, and 24 years) and alcohol use and drinking-related problems 7 years subsequently (ages 25, 28, and 31 years).

Path analytic models were relatively invariant across cohort. Across cohorts, DIS and baseline alcohol consumption related to later positive reinforcement drinking motives, but less consistency was found for the prediction of negative reinforcement motives to drink. While positive reinforcement motives were associated with greater alcohol consumption and problems 7 years later, negative reinforcement motives were generally associated with problems alone. Positive reinforcement motives for drinking mediated relations between baseline consumption and later consumption. However, results were mixed when considering DIS as a predictor and drinking problems as an outcome. Similarly, personality and baseline consumption related to later motives not to drink and such motives predicted subsequent alcohol-related problems. However, mediation was not generally supported for pathways through motives to abstain.

The results of this study replicate and extend previous longitudinal findings with youth and add to the growing literature on motivations not to engage in alcohol use.

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Request Reprint E-Mail: kristen.anderson@reed.edu

Investigating the Influence of Prenatal Androgen Exposure and Sibling Effects on Alcohol Use and Alcohol Use Disorder in Females from Opposite-Sex Twin Pairs

There are robust sex differences for alcohol phenotypes, with men reporting more drinking and alcohol use disorder (AUD) symptoms than women. However, the sources of these effects are not completely understood. Sex hormones, a substantial biological sex difference, exert neurobehavioral influences and are candidates for influencing sex differences in alcohol phenotypes. This study investigated the effects of prenatal androgens based on the hypothesis of prenatal hormone transfer, which posits that hormones from one twin influence the development of a cotwin.

This study compared female twins from opposite-sex (OSF) and same-sex (SSF) pairs to investigate associations between prenatal androgens and alcohol phenotypes. Additional analyses distinguished prenatal and postnatal effects by comparing OSFs and SSFs with a close-in-age older (CAO) brother.

OSFs endorsed more lifetime AUD symptoms than SSFs (d = 0.14). Females with a CAO brother reported greater intoxication frequency (d = 0.35), hangover frequency (d = 0.24), typical drinking quantity (d = 0.33), and max drinks (i.e., the most drinks ever consumed in a 24-hour period; d = 0.29). Controlling for postnatal effects, OSFs still endorsed more lifetime AUD symptoms than SSFs with a CAO brother (d = 0.16).

Prenatal exposure to a male cotwin was associated with increases in AUD symptoms, above the effect of postnatal exposure to a male sibling. Prenatal exposure to a male cotwwas not associated with increases in other alcohol-related phenotypes, but postnatal exposure to older male siblings produced medium effect sizes for indicators of alcohol consumption. Sex differences in AUDs, but not alcohol use, may be partially due to the neurodevelopmental effects of prenatal androgens. However, sibling effects may be larger than any
effect of prenatal androgen exposure.

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Request Reprint E-Mail: jarrod.ellingson@mail.missouri.edu

Monday, December 24, 2012

The Redistribution of Power: Neurocardiac Signaling, Alcohol and Gender

Human adaptability involves interconnected biological and psychological control processes that determine how successful we are in meeting internal and environmental challenges. Heart rate variability (HRV), the variability in consecutive R-wave to R-wave intervals (RRI) of the electrocardiogram, captures synergy between the brain and cardiovascular control systems that modulate adaptive responding.

Here we introduce a qualitatively new dimension of adaptive change in HRV quantified as a redistribution of spectral power by applying the Wasserstein distance with exponent 1 metric (W1) to RRI spectral data. We further derived a new index, D, to specify the direction of spectral redistribution and clarify physiological interpretation.

We examined gender differences in real time RRI spectral power response to alcohol, placebo and visual cue challenges.

Adaptive changes were observed as changes in power of the various spectral frequency bands (i.e., standard frequency domain HRV indices) and, during both placebo and alcohol intoxication challenges, as changes in the structure (shape) of the RRI spectrum, with a redistribution towards lower frequency oscillations.

The overall conclusions from the present study are that the RRI spectrum is capable of a fluid and highly flexible response, even when oscillations (and thus activity at the sinoatrial node) are pharmacologically suppressed, and that low frequency oscillations serve a crucial but less studied role in physical and mental health.

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Alcohol News - 52/2012

Statistics Finland (Finland) - Alcohol-related causes of death are decreasing

Alcohol-related causes have been for several years among the most common causes of death for both men and women, and the figures are high for the whole population as well. Alcohol-related deaths include both alcohol-related diseases and accidental poisoning by alcohol.

Yle Uutiset (Finland) - TS: Theme parks threatened with alcohol ban

Theme parks in Finland could in the future find it more difficult to get a license to serve alcohol if a legislative proposal is approved by parliament.

Göteborg Daily (Sweden) - Alcohol boom gate can be tested in Gothenburg

Swedish police will trial automated alcohol testing in a bid to reduce the number of alcohol affected truck drivers coming in on the ferries. Gothenburg is one of several locations being considered, according to P4 Göteborg.

The Foriegner (Norway) - Duty-free system to be spirited away

The Norwegian State has decided to try to stop what they call the “smuggling” of alcohol upon returning to this country. According to the Norwegian Telegram Bureau (NTB), the paper ticket’s demise has meant passengers have been able to obtain a double-quota, as proof of travel is now electronic instead.

Circumpolar Health (Greenland) - Alcohol in Greenland 1951-2010: consumption, mortality, prices

The effect of alcohol excise taxes and rationing upon consumption is evident. The stabilisation and subsequent decline in consumption since the mid-1990s, while alcohol prices decreased persistently, does not preclude continued effects of prices.

Skemman (Iceland) - Regrets after alcohol consumption following the 2008 financial crisis in Iceland: A prospective cohort study

In a prospective Icelandic cohort, our findings indicate that regrets after drinking decreased following the economic recession in 2008; specifically for males, those who were married or cohabiting, employed or with a university education.

Reuters UK (China) - Moutai shares lead alcohol tumble after China bans spirits from army feasts

Chinese distiller Kweichow Moutai Co Ltd 6000519.SS led a tumble in the country's alcohol sector on Monday after Beijing banned its top brass from hosting boozy banquets while working, Communist Party chief Xi Jinping's latest anti-corruption move.

UPI.com - Expanding waistlines may be due to alcohol

Those who can't lose weight despite exercising and cutting back on high-calorie food may be drinking too many calories from beverages, a U.S. dietitian says.

Payvand (Iran) - Deaths from alcohol soar in Iran

ISNA reported on Sunday December 23 that recent statistics show 92 men and nine women lost their lives due to alcohol poisoning in the past seven months, which indicates an increase of over 100 percent compared to last year.

Times of India (India) - Govt plans to introduce a sin tax to curb use of alcohol, tobacco

India has mooted the introduction of a designated "sin tax" to finance a part of the health budget during the 12th five year plan (2012-2017).

The Daily Telegraph (Australia) - Mixing alcohol and drugs a troubling trend

Just after midnight a 27-year-old man who had drunk a bottle of bourbon and five beers came to the emergency department with chest pain. In emergency medicine we have to worry about the worst possibility.

Examiner.com (USA) - Government board calls for alcohol detectors in all cars

The National Transportation Safety Board (NTSB) December 19 called for the development of passive alcohol-detection technology in cars and trucks to achieve "zero alcohol-impaired driving-related deaths."

Hindustan Times (India) - More girls experimenting with drugs, alcohol

A girl in her early twenties was admitted to a private hospital in SAS Nagar in an unconscious state about a week ago. She had mixed her alcoholic drink with a sedative, which caused difficulty in breathing and made her unconscious.

Radio Australia (Philippines) - Philippines attacks 'vices' with tobacco, alcohol tax raise

The Philippines on Thursday raised tobacco and alcohol taxes in a reform President Benigno Aquino hailed as helping to liberate "more Filipinos from the vices of smoking and drinking".

Solomon Star (Solomon Islands) - CURSE OF ALCOHOL - It’s the leading cause of traffic accidents here

ALCOHOL is the leading cause of traffic accidents during festive seasons in the last 12 years, statistics released yesterday revealed.

Express (Scotland) - SNP PLAN TO BAN BUYING ALCOHOL OVER THE INTERNET

WINE club members will be among those breaking the law under legislation planned by the SNP Government – if they take advantage of cut-price offers delivered from English warehouses.

Bangkok Post (Indonesia) - Indonesia considers total alcohol ban

Indonesian lawmakers are pushing for a ban on all alcoholic beverages throughout the archipelago that would see drinkers punished with up to two years in jail.

Medical Xpress - Excessive alcohol when you're young could have lasting impacts on your brain

Alcohol misuse in young people causes significant changes in their brain function and structure. This and other findings were recently reviewed by Dr Daniel Hermens from the University of Sydney's Brain and Mind Research Institute in the journal Cortex.

Taranaki Daily News (New Zealand) - Alcohol harm has important implications for Maori

With Christmas and New Year's celebrations approaching it's timely that we focus on the issues that contribute to binge drinking, drink-driving and the disastrous consequences for our communities.

GoodTherapy.org - How Age of Onset Predicts Drug and Alcohol Dependency

Transmissible risk refers to generational risk or family risk. Some people have a family history of physical or mental health problems, which makes them more vulnerable to developing the same problems.

Times of India (India) - WHO suggests raising liquor price to curb violence against women

Even as the national Capital remains shell shocked over the gruesome rape of the 23-year-old, the World Health Organization (WHO) has suggested clamping down on alcohol availability and raising liquor price to reduce its consumption as an important intervention to reduce violence both sexual and physical against women.

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Smoking or Alcohol Dependence Among Indigenous Australians: Treatment May Be Needed, Not Just Education

In trying to help Aboriginal and Torres Strait

Islander (Indigenous) individuals or communities to stop smoking or reduce the harms from alcohol, it is important to be aware of the strong biological basis of the drive to return to nicotine or alcohol.

In this paper we briefly describe the social and neurobiological factors that drive a dependent smoker or drinker to keep using. We set out the current range of pharmacological treatments for dependence, their role in assisting a person to either stop using or avoid relapse, and we discuss issues relating to their use in Aboriginal Australians.

There is a firm evidence base for the use of pharmacological treatments for nicotine or alcohol dependence, particularly in severe dependence or when counselling or non-pharmacological approaches have failed. Indigenous Australians should be able to access the full range of approaches to managing these conditions. Working in partnership with Indigenous health staff and agencies can help ensure that appropriate access to treatment and quality treatment delivery occurs.

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Request Reprint E-Mail: kate.conigrave@sydney.edu.au

A comparison of the anticipated and pharmacological effects of alcohol on cognitive bias, executive function, craving and ad-lib drinking

Acute alcohol administration alters automatic processing of alcohol-related cues, impairs executive functions and increases alcohol seeking. Few studies have investigated the effects of expecting to receive alcohol on these measures.

Thirty-one social drinkers completed three experimental sessions receiving either 0.65 g/kg alcohol, a placebo and a control beverage (which they knew was not alcoholic) before reporting craving and completing a test battery including a measure of automatic alcohol-approach tendencies (stimulus response compatibility task), a measure of executive function (Controlled Oral Word Association Task (COWAT)) and a taste test assessing ad-lib drinking.

Results indicated that alcohol administration impaired performance on the COWAT and increased ad-lib drinking; however, there were no significant differences on these measures after administration of placebo versus control beverages. Craving was increased after alcohol and (to a lesser extent) after placebo. Automatic alcohol-approach tendencies were pronounced after both alcohol and placebo compared to the control beverage, with no difference between alcohol and placebo.

Results suggest craving is sensitive to the anticipated and pharmacological effects of alcohol, alcohol-approach tendencies are particularly sensitive to the anticipated effects of alcohol, and measures of executive function and ad-lib drinking are affected by the pharmacological, but not the anticipated, effects of alcohol.

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Request Reprint E-Mail: prc@liverpool.ac.uk

A flicker change blindness task employing eye tracking reveals an association with levels of craving not consumption

We investigated attentional biases with a flicker paradigm, examining the proportion of alcohol relative to neutral changes detected. Furthermore, we examined how measures of the participants initial orienting of attention and of their maintained attention relate to levels of alcohol consumption and subjective craving in social drinkers.

The eye movements of 58 participants (24 male) were monitored whilst they completed a flicker-induced change blindness task using both simple stimuli and real world scenes, with both an alcohol and neutral change competing for detection.

When examined in terms of consumption levels, we observed that heavier social drinkers detected a higher proportion of alcohol related changes in real world scenes only. However, we also observed that levels of craving were not indicative of levels of consumption in social drinkers. Furthermore, also in real world scenes only, higher cravers detected a greater proportion of alcohol related changes compared to lower cravers, and were also quicker to initially fixate on alcohol related stimuli.

Thus we conclude that processing biases in the orienting of attention to alcohol related stimuli were demonstrated in higher craving compared to lower craving social users in real world scenes. However, this was not related to the level of consumption as would be expected.

These results highlight various methodological and conceptual issues to be considered in future research.

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Request Reprint E-Mail: stephen.butler@strath.ac.uk

FASD News - 51/2012

Regina Leader-Post (Canada) - Professor analysing FASD data

A University of Regina instructor hopes her research will lead to better ways of interacting with those affected by fetal alcohol spectrum disorder (FASD).

Scoop.co.nz (New Zealand) - Society 'will feel impact' of Fetal Alcohol Spectrum Disorder

A First Nations leader said fetal alcohol spectrum disorder — also known as FASD — is an "alarming" problem amongst Canada's Aboriginal population.

Shoreline Beacon (Canada) - Campaign warns against prenatal drink consumption

The Grey Bruce Health Unit and Fetal Alcohol Neurobehavioral Leadership Group have launched a coaster campaign to remind those indulging in holiday libations of the negative effects of alcohol on a developing fetus.

Scoop.co.nz (New Zealand) - Women reveal the cost of their drinking in documentary

New Zealand women reveal the cost of their drinking in documentary. “I didn’t realise my baby was as drunk as a skunk,” says Jackie, a married Hawke’s Bay mother of three, talking about the effect drinking while she was pregnant has had on her young son.

San Francisco Chronicle (USA) - SD program aims to curb fetal alcohol syndrome

South Dakota's largest medical facility and the Oglala Sioux Tribe have announced a partnership to expand a program aimed at preventing fetal alcohol syndrome and other alcohol-related problems affecting Native American children by intervening before their mothers become pregnant.

RESOURCES and VIDEOS

FASD Think Tank - Over 100 Holiday Strategies for Fetal Alcohol Spectrum Disorders Supporting yourself and your family

Holidays are a tough time for our kids. We may place pressure on ourselves to try to make holidays perfect. What matters is family and love and learning to live and appreciate each other for our unique gifts.

NOFAS - Nicholas (age 9) on living with FASD

The National Organization on Fetal Alcohol Syndrome (NOFAS) is the leading voice and resource of the Fetal Alcohol Spectrum Disorders (FASD) community.

NOFAS - Nancy Roget on FASD - Frontier Regional FASD Training Center

The National Benefit Authority - CARING FOR A BABY WITH FETAL ALCOHOL SPECTRUM DISORDER

Fetal alcohol spectrum disorder (FASD), a health condition that is caused when women ingest alcohol during pregnancy, has been Disability Living’s topic of discussion for the past week.'

UPCOMING

Government of Alberta - FASD Learning Series 2012-13

FASD Trust Event Calendar - UK

RESEARCH

ScienceAlerts - Global Functional Connectivity Abnormalities in Children with Fetal Alcohol Spectrum Disorders

Previous studies, including those employing diffusion tensor imaging (DTI), have revealed significant disturbances in the white matter of individuals with fetal alcohol spectrum disorders (FASD).

Saturday, December 22, 2012

Alcohol and student performance: Estimating the effect of legal access

We consider the effect of legal access to alcohol on student achievement.

Our preferred approach identifies the effect through changes in one's performance after gaining legal access to alcohol, controlling flexibly for the expected evolution of grades as one makes progress towards their degree.

We also report RD-based estimates but argue that an RD design is not well suited to the research question in our setting.
We find that students’ grades fall below their expected levels upon being able to drink legally, but by less than previously documented.

We also show that there are effects on women and that the effects are persistent.

Using the 1997 National Longitudinal Survey of Youth, we show that students drink more often after legal access but do not consume more drinks on days on which they drink.

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Request Reprint E-Mail: jlindo@uoregon.edu

Research Article REPORTS OF DRINKING TO SELF-MEDICATE ANXIETY SYMPTOMS: LONGITUDINAL ASSESSMENT FOR SUBGROUPS OF INDIVIDUALS WITH ALCOHOL DEPENDENCE

Self-medication with alcohol is frequently hypothesized to explain anxiety and alcohol dependence comorbidity. Yet, there is relatively little assessment of drinking to self-medicate anxiety and its association with the occurrence or persistence of alcohol dependence in population-based longitudinal samples, or associations within demographic and clinical subgroups.

Hypothesizing that self-medication of anxiety with alcohol is associated with the subsequent occurrence and persistence of alcohol dependence, we assessed these associations using data from the National Epidemiologic Survey on Alcohol and Related Conditions, and examined these associations within population subgroups. This nationally representative survey of the US population included 43,093 adults surveyed in 2001–2002, and 34,653 reinterviewed in 2004–2005. Logistic regression incorporating propensity score methods was used.

Reports of drinking to self-medicate anxiety was associated with the subsequent occurrence (adjusted odds ratio (AOR) = 5.71, 95% confidence interval (CI) = 3.56–9.18, P < .001) and persistence (AOR = 6.25, CI = 3.24–12.05, P < .001) of alcohol dependence. The estimated proportions of the dependence cases attributable to self-medication drinking were 12.7 and 33.4% for incident and persistent dependence, respectively. Stratified analyses by age, sex, race-ethnicity, anxiety disorders and subthreshold anxiety symptoms, quantity of alcohol consumption, history of treatment, and family history of alcoholism showed few subgroup differences.

Individuals who report drinking to self-medicate anxiety are more likely to develop alcohol dependence, and the dependence is more likely to persist. There is little evidence for interaction by the population subgroups assessed. Self-medication drinking may be a useful target for prevention and intervention efforts aimed at reducing the occurrence of alcohol dependence.

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Request Reprint E-Mail: rcrum@jhsph.edu

The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model

Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment.

In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 h on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133.

The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol.

These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders.

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Request Reprint E-Mail: swashburn@cvm.tamu.edu

Reduction of alcohol intake by the positive allosteric modulator of the GABAB receptor, rac-BHFF, in alcohol-preferring rats

Previous research has demonstrated that treatment with the positive allosteric modulator (PAM) of the GABA_B receptor (GABA_B PAM), rac-BHFF, suppressed lever-responding for alcohol and amount of self-administered alcohol in Sardinian alcohol-preferring (sP) rats.

The present study was designed to extend the investigation on the anti-alcohol effects of rac-BHFF to alcohol drinking behavior. To this end, sP rats were exposed to the homecage, 2-bottle “alcohol (10%, v/v) vs water” choice regimen, with unlimited access for 24 h/day. rac-BHFF was administered once daily and for 7 consecutive days at the doses of 0, 50, 100, and 200 mg/kg (i.g.).

Treatment with rac-BHFF resulted in an immediate, stable, and dose-related reduction in daily alcohol intake; the overall magnitude of reduction in alcohol intake averaged approximately 25%, 40%, and 65% in 50, 100, and 200 mg/kg rac-BHFF-treated rat groups, respectively. An increase in daily water intake fully compensated the reduction in alcohol intake, so that daily total fluid intake was unaffected by treatment with rac-BHFF. Daily food intake tended to be reduced only by the highest dose of rac-BHFF.

These results complement closely with previous data indicating that (a) rac-BHFF suppressed operant, oral alcohol self-administration in sP rats and (b) the prototypic GABA_B PAMs, CGP7930 and GS39783, reduced alcohol drinking in sP rats.

However, while the reducing effect of CGP7930 and GS39783 on the daily alcohol intake tended to vanish after the first 2–3 days of treatment, the reducing effect of rac-BHFF on daily alcohol intake remained unchanged over the entire 7-day treatment period.

These data strengthen the hypothesis that GABA_B PAMs may represent a step forward in the search for GABA_B receptor ligands with therapeutic potential for alcoholism.

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Request Reprint E-Mail: colomb@unica.it

Impulsivity partially mediates the association between reduced working memory capacity and alcohol problems

Although alcohol use disorders (AUDs) have been associated with impulsive personality traits and reduced working memory capacity (WMC), less is known about the nature of their interrelationships.

This study was designed to test the hypothesis that low WMC is associated with both impulsive personality and alcohol problems, and that impulsive personality mediates the association between low WMC and alcohol problems.

Measures of impulsive personality, WMC, and alcohol problems were assessed in a sample of young adults (N = 474), that varied widely in severity of alcohol problems, 57% of whom had alcohol dependence.

Simple correlations revealed that WMC, impulsive personality traits, and alcohol problems were all significantly related. Structural equation models (SEMs) showed that impulsivity partially mediated the association between WMC and alcohol problems.

Although directionality cannot be determined from these cross-sectional data, the results suggest that reduced WMC may promote impulsivity, which in turn, predisposes to alcohol problems.

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Request Reprint -Mail: finnp@indiana.edu

Opioids in the perifornical lateral hypothalamus suppress ethanol drinking

The opioid system is known to enhance motivated behaviors, including ethanol drinking and food ingestion, by acting in various reward-related brain regions, such as the nucleus accumbens, ventral tegmental area and medial hypothalamus. There is indirect evidence, however, suggesting that opioid peptides may act differently in the perifornical lateral hypothalamus (PF/LH), causing a suppression of consummatory behavior.

Using brain-cannulated Sprague–Dawley rats trained to voluntarily drink 7% ethanol, the present study tested the hypothesis that opioids in the PF/LH can reduce the consumption of ethanol, with animals receiving PF/LH injections of the δ-opioid receptor agonist D-Ala2-met-enkephalinamide (DALA), the μ-receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), the κ-receptor agonist (±)-trans-U-50,488 methanesulfonate (U-50,488H), or the general opioid antagonist methylated naloxone (m-naloxone). The consumption of ethanol, lab chow, and water was monitored for 4 h after injection. The results showed that the three opioid receptor agonists injected into the PF/LH specifically and significantly reduced ethanol intake, while causing little change in chow or water intake, and the opposite effect, enhanced ethanol intake, was observed with the opioid antagonist.

Of the three opioid agonists, the δ-agonist appears to produce the most consistent and long-lasting suppression of consumption. This effect was not observed with injections 2 mm dorsal to this area, focusing attention on the PF/LH as the main site of action.

These results suggest that the opioid peptides have a specific role in the PF/LH of reducing ethanol drinking, which is distinct from their more commonly observed appetitive actions in other brain areas. The additional finding, that m-naloxone in the PF/LH stimulates ethanol intake in contrast to its generally suppressive effect in other regions, focuses attention on this hypothalamic area and its distinctive role in contributing to the variable effects sometimes observed with opioid antagonist therapy for alcoholism.

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Request Reprint E-Mail: leibow@mail.rockefeller.edu

Dissociable brain signatures of choice conflict and immediate reward preferences in alcohol use disorders

Impulsive delayed reward discounting (DRD) is an important behavioral process in alcohol use disorders (AUDs), reflecting incapacity to delay gratification. Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD, but applications of neuroeconomics in relation to AUDs have been limited.

This study examined the neural mechanisms of DRD preferences in AUDs, with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict.

Heavy drinking adult men with (n = 13) and without (n = 12) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan. Participant responses were coded based on choice type (impulsive versus restrained) and level of cognitive conflict (easy versus hard).

AUD+ participants exhibited significantly more impulsive DRD decision-making. Significant activation during DRD was found in several decision-making regions, including dorsolateral prefrontal cortex (DLPFC), insula, posterior parietal cortex (PPC), and posterior cingulate. An axis of cognitive conflict was also observed, with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area. AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control (DLPFC) and prospective thought (PPC) and exhibited less task-related deactivation of areas associated with the brain's default network during DRD decisions.

This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs.

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Request Reprint E-Mail: jmackill@uga.edu

Fronto-striatal functional connectivity during response inhibition in alcohol dependence

Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways.

This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto-striatal networks during response inhibition in an alcohol-dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the μ-opioid receptor (OPRM1) gene.

Twenty individuals with alcohol dependence (six females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level-dependent functional magnetic resonance imaging while performing a Stop-Signal Task. The relationship between alcohol dependence severity and functional connectivity within fronto-striatal networks important for response inhibition was assessed using psychophysiological interaction analyses.

Analyses revealed greater alcohol dependence severity was associated with weaker functional connectivity between the putamen and prefrontal regions (e.g. the anterior insula, anterior cingulate and medial prefrontal cortex) during response inhibition. Furthermore, the OPRM1 genotype was associated with differential response inhibition-related functional connectivity.

This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto-striatal pathway underlying response inhibition is weakened as alcoholism progresses.

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Request Reprint E-Mail: lararay@psych.ucla.edu

Aims

Wednesday, December 26, 2012

Monday, December 24, 2012

Saturday, December 22, 2012