Nevertheless, the fact that the DAT genotype might influence naltrexone response or interact with the OPRM1 receptor has intuitive appeal. It has been speculated, and partially supported, that the dopamine transporter coded by the genotype with at least one 9 VNTR is less effective/functional than the one coded by the 10/10 VNTR genotype (Fuke et al., 2001). Since the dopamine transporter removes dopamine from the synaptic cleft, a “loss-of-function” genotype would allow more dopamine availability after pre-synaptic release. Theoretically, this should produce more reward and reinforcement and, perhaps, more stimulation. It has been reported that individuals with at least one DAT 9 VNTR genotype have a greater brain reward system response to reward anticipation and receipt during fMRI paradigms (Dreher et al., 2009; Forbes et al., 2009) and also a greater ventral striatal responses to smoking cues (Franklin et al., 2009; Franklin et al., 2011). To our knowledge this has not been explored in alcoholics and there has not been an attempt to evaluate the combined effects of DAT and OPRM1 genetic differences simultaneously.
