Mague, Isiegas, Huang et al. (2009) generated a mutant mouse line that possessed the mouse equivalent (A112G, N38D) of the human SNP for studying the mechanisms underlying the changes associated with OPRM1 A118G SNP in humans. The mice homozygous for G112 allele (G/G mice) displayed reduced antinociceptive responses to morphine than those homologous for A112 allele (A/A mice) (Mague et al., 2009), similar to the results in humans. In addition, G/G mice showed reduced morphine-induced hyperactivity and locomotor sensitization (Mague et al., 2009). Moreover, female, not male, G/G mice failed to show a conditioned place preference to morphine-paired environments (Mague et al., 2009). Recently, Ramchandani et al. (2011) have also generated a mouse model of the OPRM1 A118G SNP by replacing the mouse exon 1 with the human exon 1 carrying the A118 or G118 allele. They found that homozygous G118 mice showed a 4-fold greater peak dopamine response to an alcohol challenge as homozygous A118 mice. Furthermore, Mahmoud, Thorsell, Sommer et al. (2011) reported that the potency and efficacy of morphine in modulating Ca2+ channels were reduced in sensory neurons of mice expressing the 118 GG gene compared with those expressing the 118AA version.
