Rhesus macaques (Maccaca mulatta) offer a unique opportunity for translational research given the presence of a non-synonymous SNP (OPRM1 C77G) resulting in an amino acid change (Arg26Pro), which in turn was found to confer a 3.5 increase in binding affinity for β-endorphin (Miller et al., 2004). This polymorphism is functionally similar to the Asn40Asp SNP in humans. Studies have shown that male macaques carrying the OPRM1 77G allele displayed increased alcohol-induced stimulation as well as higher alcohol preference and consumption, compared to OPRM1 77C homozygotes (Barr et al., 2007). The sex-specificity of the effect is contrary to the mouse models, where female carriers of the G112 allele displayed an altered behavioral response to acute morphine withdrawal (Mague et al., 2009). It is hypothesized that hormonal modulation may have an effect on this phenotype and could be experimentally manipulated in preclinical models to further investigate a sex by genotype interaction of this SNP.
