We found that A112G SNP led to reduced DAMGO-stimulated [35S]GTPγS binding only in the VTA when data of male and female mice were combined. In contrast, our previous studies revealed that A112G SNP resulted in lower MOPR expression in several brain regions, including VTA, cortices, NAc, hypothalamus, amygdala, PAG, and superficial layers of the superior colliculus (Wang et al., 2012). Our data indicate that changes in DAMGO-stimulated [35S]GTPγS binding levels do not correlate with alterations in MOPR levels. A similar lack of a close correlation has been observed between mu, kappa or cannabinoid receptor and G protein activation (Breivogel, Sim, and Childers, 1997; Vogt, Sim-Selley, Childers et al., 2001; Wang et al., 2011). The mechanisms underlying these discrepancies are not yet clear, but some factors may be involved. The ratios of receptor to G proteins may vary among brain regions. MOPRs have been shown to activate different types of G proteins (Chakrabarti, Prather, Yu et al., 1995), which may lead to different numbers of G proteins activated per receptor in different regions. It is also possible that some MOPRs may not be coupled functionally, due to their intracellular location (Wang, Van Bockstaele, and Liu-Chen, 2008).
