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Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans.

ABSTRACT: Koob's allostatic model of addiction emphasizes the transition from positive reinforcement to negative reinforcement as dependence develops. This study seeks to extend this well-established neurobiological model to humans by examining subjective response to alcohol (SR) as a biobehavioral marker of alcohol reinforcement. Specifically, this study examines (a) differential SR in heavy drinkers (HDs) vs. alcohol dependent individuals (ADs) and (b) whether HDs and ADs differ in terms of the association between SR and craving.Data was culled from two alcohol challenge studies, totalling 91 participants (oversampled on OPRM1 Asp40 carriers). Alcohol was administered intravenously and participants completed standard measures of SR and craving at BrAC's of 0.02, 0.04, and 0.06 g/dl. SR was modeled as a multi-dimensional construct consisting of stimulation, sedation, and tension relief.ADs reported significantly higher sedation and craving initially and exhibited a blunted response to alcohol along escalating BrACs. ADs exhibited greater initial tension but did not differ from HDs in tension reduction across rising BrACs. Further, alcohol-induced stimulation was associated with alcohol craving to a significantly greater degree in HDs, as compared to ADs.This study provides initial evidence that HDs and ADs differ in their subjective experience of alcohol and in the association between dimensions of SR and craving for alcohol. Hypotheses derived from the allostatic model were partially supported, such that, while ADs and HDs did not differ on stimulation response, there was a relative dissociation between positive reinforcement and craving in ADs as compared to HDs.

SUBMITTER: Bujarski S

PROVIDER: S-EPMC4169206 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans.

Bujarski Spencer S Ray Lara A LA

Drug and alcohol dependence 20140428

<h4>Background</h4>Koob's allostatic model of addiction emphasizes the transition from positive reinforcement to negative reinforcement as dependence develops. This study seeks to extend this well-established neurobiological model to humans by examining subjective response to alcohol (SR) as a biobehavioral marker of alcohol reinforcement. Specifically, this study examines (a) differential SR in heavy drinkers (HDs) vs. alcohol dependent individuals (ADs) and (b) whether HDs and ADs differ in te ...[more]

PMID: 24837580

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Project description:BackgroundPharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an α4β2-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored.MethodsIn this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2 mg/d) or placebo. After 2 weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80 mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined.ResultsResults indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90 days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol.ConclusionsOur results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.

Dataset Information

Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans.

Publications

Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans.

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