Irrespectively of its possible role as a susceptibility factor, excessive reward-related DA-response to alcohol in carriers of OPRM1 118G might be of pharmacogenetic importance in treatment of excessive alcohol use. Indeed, two studies have found that the presence of the 118G allele was associated with a therapeutic response to the opioid antagonist naltrexone 50,51. Although one study failed to find such an effect 52, recent non-human primate data provide strong evidence for this notion under closely controlled experimental conditions 53. Our data are consistent with a selective role of endogenous opioids for alcohol reward in OPRM1 118G carriers, and provide a possible biological mechanism for the preferential naltrexone response in this population. However, the dissociation between objective measures of alcohol-induced DA-release and subjective reports of alcohol effects may argue against a simplistic view of alcohol-induced DA-release as an immediate mediator of drug reward. Instead, these data may be more compatible with a view of ventral striatal DA-activation as a signal predictive of alcohol reward, and perhaps involved in learning processes important for addiction 54. Of note, the level of alcohol-induce
