The Effect of Naltrexone on Alcohol’s Stimulant Properties and Self-Administration Behavior in Social Drinkers: Influence of Gender and Genotype

Authors

  • Elaine Setiawan,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Robert O. Pihl,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Sylvia M. L. Cox,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Christina Gianoulakis,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Roberta M. Palmour,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Chawki Benkelfat,

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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  • Marco Leyton

    1. From the Department of Neurology and Neurosurgery (ES, SMLC, CB, ML); Department of Psychology (ROP, ML); and Department of Psychiatry (ROP, CG, RMP, CB, ML), McGill University, Montréal, QC, Canada.
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Reprint requests: Marco Leyton, PhD, Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. Tel.: 514-398-5804; Fax: 514-398-4866; E-mail:marco.leyton@mcgill.ca

Abstract

Background:  Few pharmacological treatments for alcohol dependence are available. Moreover, the best supported treatment, naltrexone hydrochloride, appears to work for only some.

Methods:  To investigate potential predictors of these differential responses, 40 social drinkers (20 women) were administered 6 days of treatment with naltrexone vs. placebo in a double-blind, counterbalanced, crossover design. At the end of each treatment period, participants received a single dose of their preferred alcoholic beverage followed by the opportunity to work for additional alcohol units using a progressive ratio (PR) breakpoint paradigm. All subjects but one were genotyped for the A118G polymorphism of the mu opioid receptor gene (OPRM1).

Results:  Naltrexone decreased the ethanol-induced ‘euphoria’ to a priming dose of alcohol in two subgroups: (i) in women, and (ii) in subjects with the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone did not decrease motivation to work for additional alcoholic beverages on the PR task regardless of gender or genotype.

Conclusions:  The results add to the evidence that naltrexone decreases positive subjective effects of alcohol, with preferential effects in distinct subgroups. Similar effects in heavier drinkers might decrease alcohol use.

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