Taken together, our data strongly support a causal role of the OPRM1 118G allele to confer a more vigorous DA response to alcohol in the ventral striatum. These findings may be related to observations of differential subjective alcohol effects as a function of OPRM1 A118G genotype in humans 12, and of markedly increased psychomotor responses to alcohol in rhesus males carrying the functionally equivalent 77G variant 14. Interestingly, we also found that subjective feelings of intoxication over time differed as a function of genotype. Carriers of the 118G allele showed signs of rapid acute tolerance, similar to that previously described in men at genetic risk for alcoholism 41. The use of a reverse-translational approach allowed us to effectively isolate the influence of the human 118G variant from that of other polymorphisms with which it might be in LD.
