Clinical and preclinical data provide strong evidence that the rewarding and aversive effects of alcohol are mediated via interactions between opioid and dopamine systems. Acute alcohol induces release of endorphins and stimulates dopamine release in the nucleus accumbens, both of which correlate with subjective responses to alcohol (Volkow et al., 2017). Dopaminergic neurotransmission in the nucleus accumbens is regulated by the DAT and opioid inputs, and such interactions are thought to contribute to the positive and aversive subjective effects of alcohol, and patterns of alcohol consumption. Indeed, prior studies have shown decreased DAT1 expression and lower DAT availability in DAT1 A9 carriers than A10 homozygotes, consistent with increased dopaminergic tone in A9 carriers (Mill et al., 2002, Fuke et al., 2001, Heinz et al., 2000). The OPRM1 *G allele is associated with lower global mu-opioid receptor availability (Ray et al., 2011, Weerts et al., 2013) and greater dopamine release in response to alcohol (Ramchandani et al., 2011), cigarette smoking (Domino et al., 2012), or pain (Pecina et al., 2015) challenges. The stimulatory effects of acute alcohol are also associated with
