In the VTA, G/G mice (males and females pooled) exhibited significantly higher basal [35S]GTPγS binding than A/A mice. In most of the other regions, G/G mice showed a trend of higher basal levels, but they did not reach statistical significance. Previously Mague et al. (2009) reported lower MOPR protein levels by immunoblotting and lower Bmax value of [3H]DAMGO binding to the MOPR in the brains of G/G mice, compared to A/A mice. We also found that A/A mice displayed higher MOPR expression than G/G mice in both males and females (Wang et al., 2012). Therefore, the higher basal [35S]GTPγS binding in G/G mice is not due to differences in the MOPR level. Basal [35S]GTPγS binding may represent constitutive (agonist-independent) activation of Gα subunits of trimeric G proteins and many other guanine nucleotide binding proteins present in the brain. Differences in levels and activities of these guanine nucleotide binding proteins may contribute to the differences in basal [35S]GTPγS binding between A/A and G/G mice. It has also been shown that [35S]GTPγS binding to NDPK accounts for part of the high basal binding (Zhang, Li, Chen et al., 1999).
