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Tuesday, September 15, 2009

Suppression of Alcohol Preference by Naltrexone in the Rhesus Macaque: A Critical Role of Genetic Variation at the μ-Opioid Receptor Gene Locus
Biological Psychiatry Article in Press, 12 Sep 2009

The role of a nonsynonymous A118G polymorphism of the human μ-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.

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.

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


Request Reprint E-Mail: markus.heilig@mail.nih.gov

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