In summary, A112G affected DAMGO-stimulated [35S]GTPγS binding in region- and sex-specific manners. A112G SNP led to reduced DAMGO-stimulated [35S]GTPγS binding in the VTA, which may be associated with lower morphine-induced hyperactivity and locomotor sensitization. There are sex differences in the effects of A112G SNP in NAc core that may contribute to lack of morphine-induced conditioned place preference in female G/G mice. In G/G mice males showed significantly higher net DAMGO-stimulated [35S]GTPγS binding than females in some brain areas, of which the in vivo pharmacological consequences remain to be examined.