The association between genetic variation of OPRM1 and the response to alcohol is supported by results obtained by using animal models mimicking the A118G (Asn40Asp) variation. A recent study showed that in the brain areas central for drug reward, alcohol-induced dopamine release was restricted to individuals carrying the 118G allele (Ramchandani et al., 2011). The authors further confirmed these results by generating humanized mouse lines carrying the different alleles of the human OPRM1 and performing brain microdialysis studies, which showed a 4-fold greater peak of dopamine response to an alcohol challenge in mice carrying the G allele when compared with mice with the A allele (Ramchandani et al., 2011). In rhesus monkeys, the OPRM1 gene harbors a natural SNP polymorphism, C77G, that appears to be functionally similar to the human A118G polymorphism (Barr et al., 2004). The variant allele has been shown to exhibit similar physiological responses when compared with the human polymorphism including a 3.5-fold elevated affinity of the G77 allele encoded protein for β-endorphin (Miller et al., 2004) comparable with the 3-fold increased binding reported for the 118G
