To delineate the mechanisms underlying the changes associated with the OPRM1 A118G SNP in humans, Mague et al. [18] generated a knock-in mouse line that possesses the mouse equivalent of the A118G variant in the hMOPR gene (Oprm1 A112G). Mice homozygous for the G112 allele (G/G mice) had lower antinociceptive responses to morphine than mice homozygous for the A112 allele (A/A mice) [18], indicating that these mice represent good animal models for studying the A118G SNP of the MOPR in humans. In addition, G/G mice showed greatly attenuated morphine-induced hyperactivity, and impaired development of locomotor sensitization [18]. Moreover, female, but not male, G/G mice exhibited reductions in the rewarding properties of morphine and the aversive components of naloxoneprecipitated morphine withdrawal [18]. More recently, Ramchandani et al.[19] established two mouse lines with humanized mouse MOPR genes (h/mMOPR), where the mouse Oprm1 exon 1 was replaced by the corresponding human sequence and carried the A118 or G118 allele. Using brain microdialysis, they found a 4-fold greater peak dopamine response to an alcohol challenge in G118-h/mMOPR than in A118-h/mMOPR mice [19]. This is
