pharmacological, molecular, and behavioral significance of this polymorphism. A knock-in mouse model harboring the equivalent point mutation in the mouse, the A112G, which alters the same amino acid coding from an asparagine to aspartic acid at position 38 (Asn38Asp; N38D), was recently developed (Mague et al., 2009). Studies of this novel mouse model suggested that mice carrying this SNP (A112G) demonstrated phenotypic similarities to humans carrying the Asp40 allele, such as reduced OPRM1 mRNA expression, lower OPRM1 receptor protein levels, and reduced morphine-induced analgesia (Mague et al., 2009). Importantly, this study highlighted sex-dependent effects and suggested that the functional consequences of this SNP cannot be evaluated as a simple loss or gain of function and instead may be circuitry-dependent. A second approach to model this SNP generated 2 mouse lines that expressed humanized receptors with either the Asn or Asp variant (Ramchandani et al., 2011). In this study, mice with the Asp variant demonstrated a 4-fold greater peak striatal DA response to alcohol administration compared to mice with the Asn variant. Together, these preclinical models have allowed for the replication of important phenotypes across species and these translational efforts provide a promising avenue for future studies, including animal models of
