they remain controversial (Mague and Blendy. 2010; Yuferov et al. 2010; Walter and Lotsch 2009; Arias et al. 2006; Ray et al. 2011). To examine the effects of this polymorphism on behavior while maintaining an isogenic environmental and genetic background, a mutation was made at the equivalent position in the mouse Oprm1 gene (Mague et al. 2009). These G/G mice showed reduced Oprm1 mRNA and protein levels (consistent with the loss-of-function hypothesis); reduced locomotor sensitivity in response to morphine and reduced anti-nociception on the hot plate test in response to morphine; these differences were consistent with some previous observations in humans. Taking a slightly different approach, a mouse with the SNP containing exon knocked in was also generated (Ramchandani et al. 2011). This study focused on the modulation of dopamine release following ethanol administration in both humans and mice. Using positron emission tomography and [11C]-raclopride displacement in humans and micro-dialysis in mice, they showed that the G allele was associated with greater dopamine release in response to ethanol in both species. Interestingly, Ramchandani et al. (2011) did not observe a difference in receptor binding between the two lines. Taken together, these findings suggest that this SNP is especially likely to
