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Biol Psychiatry. 2010 Jan 1;67(1):78-80. doi: 10.1016/j.biopsych.2009.07.026.

Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus.

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  • 1Laboratory of Clinical and Translational Studies, National Institutes of Health (NIH)/National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland 20892-1108, USA.

Abstract

BACKGROUND:

The role of a nonsynonymous A118G polymorphism of the human micro-opioid receptor gene (OPRM1) for alcohol reward and therapeutic efficacy of naltrexone remains controversial. A functionally equivalent OPRM1 C77G polymorphism in rhesus macaques allows this to be addressed under controlled experimental conditions.

METHODS:

Twenty-one rhesus macaques (13 female rhesus macaques, 8 male rhesus macaques) were genotyped for OPRM1 C77G and studied during 1-hour sessions for preference between an aspartame-sweetened alcohol solution (8.4% vol/vol) and a nonalcoholic control fluid in a baseline session followed by naltrexone (1 mg/kg) and vehicle treatment in a counterbalanced within-subject design.

RESULTS:

Mixed-model analysis of variance controlling for baseline and sex showed a highly significant (p = .003) interaction between genotype and treatment. Post hoc analysis showed that vehicle-treated 77G carriers had markedly higher alcohol preference than 77C homozygous subjects (p = .001). Following naltrexone administration, 77G carriers decreased their preference (p = .002) and no longer differed from 77C homozygous subjects. In contrast, the latter group was unaffected by treatment and, in fact, showed a trend-level increase of preference following naltrexone.

CONCLUSIONS:

These results support a critical pharmacogenetic role of OPRM1 variation for therapeutic efficacy of naltrexone.

PMID:
19748082
[PubMed - indexed for MEDLINE]
PMCID:
PMC2794913
Free PMC Article

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