Indeed, there is some evidence for functional interactions of the OPRM1 gene and the DA system. In human PET studies, striatal DA response to alcohol administration was limited to OPRM1 G carriers (Ramchandani et al., 2011); a similar response to smoked nicotine was observed (Domino et al., 2012). These studies did not evaluate DAT1 A9 vs A10 genotypes. Two recent exploratory studies provide some evidence for epistatic interactions between these two polymorphisms. Specifically, non-treatment seeking alcoholics who were carriers of both OPRM1 AA and DAT1 A9 alleles showed greater alcohol-induced stimulation to oral alcohol administration in a lab-bar, and improved drinking outcomes in response to naltrexone treatment (Anton et al., 2012). The second study in non-treatment seeking heavy drinkers reported that OPRM1 G carriers who were also DAT1 A10 homozygotes had steeper increases in alcohol-induced stimulation and vigor (Ray et al., 2014). Clearly, additional studies are needed to understand the independent vs. epistatic effects of DAT1 and OPRM1 genotypes.
