Influence of OPRM1 genotype on induction and maintenance of alcohol drinking in monkeys

Abstract

Studies in humans indicate that specific single nucleotide polymorphisms (SNPs) in the gene encoding the μ‐opioid receptor (OPRM1) may influence sensitivity to the abuse‐related effects of alcohol. Rhesus macaques express a functionally analogous SNP (C77G) and serve as a highly translational model of the human variant. We selected rhesus macaques (n=18) a priori such that the genotypes (G/G, C/G, C/C) were equally represented, and characterized alcohol pharmacokinetics and self‐administration behavior via established oral induction paradigms. Preliminary results suggest that G/G animals met drinking criteria sooner and more often during the induction period than C/C animals. We then evaluated their sensitivity to the reinforcing effects of alcohol by varying the concentration available (1–8%) for self‐administration during a 3‐hr daily access period. All animals maintained stable intakes with little variation in dose ingested across different alcohol concentrations. G‐allele carriers drank significantly higher doses of alcohol across the different concentrations. No significant pharmacokinetic differences between genotypes were observed. These data suggest that the G‐allele in macaques may increase alcohol drinking behavior, potentially modeling a pharmacogenetically‐determined vulnerability to alcohol use disorders in humans. Funding: AA016828 (DMP) and RR000168 (NEPRC; OD011103)