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Chunk #3 — Introduction

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Brain region- and sex-specific alterations in DAMGO-stimulated [(35) S]GTPγS binding in mice with Oprm1 A112G.
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We have demonstrated that mice with oprm1 A112G displayed lower MOPR expression in some, but not all, brain regions (Wang, Huang, Ung et al., 2012). The effects of A112G on MOPR protein expression have sex differences in some brain regions (Wang et al., 2012). In the mouse brains A112G reduced N-glycosylation of the MOPR and in cultured cells A118G in the human MOPR decreased N-glycosylation and protein stability (Huang et al., 2012). The reduction in MOPR expression in brain regions by the A112G (Wang et al., 2012) is likely to be involved in attenuated morphine-induced antinociception, hyperactivity and locomotor sensitization (Mague et al., 2009). The observed behavioral changes in A112G mice may also be due to alterations in MOPR-G protein coupling, in addition to changes in MOPR level. In the present study, we investigated whether A112G SNP affected MOPR-mediated G protein activation among brain regions by quantitative in vitro autoradiography of DAMGO-stimulated [35S]GTPγS binding.