One advantage of the current paradigm is the potential for improved consilience with animal models, which often favor operant self-administration procedures (Kalant, 2010; Leeman et al., 2010; Zimmermann et al., 2013). From this perspective it is notable that the current findings converge with nonhuman primate studies examining the OPRM1 C77G polymorphism, considered functionally analogous to the human A118G variant. Specifically, rhesus monkeys with the 77G variant (proposed as a functional equivalent to 118G) displayed higher alcohol self-administration under simple operant and free access paradigms (Barr et al., 2007; Vallender et al., 2010). Jointly, these findings suggest a preference for higher self-imposed brain alcohol exposure among 118G/77G carriers under controlled conditions. The literature on OPRM1 includes other evidence for cross-species convergence, including associations with alcohol-induced striatal dopamine release (Heilig et al., 2011; Ramchandani et al., 2011) and differential reduction of alcohol consumption during treatment with the μ-opioid receptor antagonist naltrexone (Oslin et al., 2003; Vallender et al., 2010). These instances of cross-species replication are particularly important for inferring a functional role of OPRM1 for certain neurobiological and pharmacogenetic outcomes (Barr et al., 2010; Heilig et al., 2011).
