Since the A112G SNP alters MOPR expression, some of the behavioral outcomes could be explained by the reduction in protein levels. Indeed, studies investigating opioid responses in MOPR knockout heterozygous mice have found similar reductions in morphine-mediated antinociception using tail flick and hot plate tests (Sora et al., 1997) and sex-specific decreases in alcohol reward using voluntary ethanol consumption and place-conditioning paradigms (Hall et al., 2001). However, these sex-specific differences in ethanol reward were due in large part to elevated responses in wild type female mice compared to wild type male mice, with little differences reported between male and female heterozygous mice. Indeed in wild type male mice, no ethanol preference was observed; therefore, it is difficult to assess whether or not heterozygous MOPR knockout males displayed ethanol reward deficits. In addition to reducing expression levels, it should be emphasized that one consequence of the A112G knockin mouse (and the A118G SNP) is the deletion of an N-linked glycosylation site. Glycosylation plays a role in receptor sorting, expression, trafficking, ligand binding, and signal transduction (Fan et al., 1997; Rathz et
