Of note, and consistent with this hypothesis, naltrexone has been shown to block the release of dopamine in the nucleus accumbens in animals (Gonzales and Weiss, 1998; Middaugh and Bandy, 2000; Ramchandani et al., 2011) and also ventral striatal activation to alcohol cues in man (Myrick et al., 2008). If a person also has a loss-of-function dopamine transporter gene i.e. at least one 9 VNTR, then it would be those very people that might respond most robustly to the dopamine reducing effects of naltrexone. They would be the most “reward sensitive” to alcohol and would get a reciprocal down regulation in dopamine-induced alcohol stimulation while taking naltrexone, translating into less stimulation and less drinking. Why this should not occur more strongly in asp40 OPRM1 genotype individuals (the ones that had been thought to be most naltrexone responsive) is not clear. However, as stated previously, there might be either developmental issues, and/or brain regional effect differences etc. that are not completely understood at this time.
