A subsequent translational study found important evidence for a functional association of A118G with neurobiological responses to alcohol (Ramchandani et al., 2011). This study used positron emission tomography to confirm enhanced alcohol-induced striatal dopamine release in 118G carriers, also demonstrating a similar result in rodent lines with a humanized OPRM1 sequence in which the A118G SNP was experimentally manipulated (Ramchandani et al., 2011). Importantly, the latter finding can be interpreted as supporting a functional role of A118G in alcohol-induced dopamine response (Heilig et al., 2011). Despite the apparent association of OPRM1 with measures of alcohol-related reward, the relevance of these findings for alcohol use behavior remains controversial given mixed evidence in studies focusing on self-reported drinking or diagnostic status (Arias et al., 2006; Kranzler et al., 2013). Laboratory self-administration paradigms offer a viable context for addressing this question, but human studies are few. Initial studies examining OPRM1 in the context of oral self-administration paradigms found no genotype differences in self-administration (Anton et al., 2012; Setiawan et al., 2011).
