In addition to a role for Alk in the acute response to ethanol, we found that Alk regulates ethanol consumption in mice. Not only does reduced Alk expression in the striatum of BXD recombinant inbred mice correlate with increased ethanol intake in a two-bottle choice protocol, but global loss of ALK function (in AlkKO mice) leads to increased ethanol consumption in a limited-access binge drinking paradigm. We hypothesize that reduced ALK expression or function in humans (perhaps in individuals carrying minor alleles) might lead to increased ethanol consumption. Although not directly addressed in the current studies, low LR to ethanol in humans is correlated with increased risk for developing AUDs [2], [33]. We found 4 SNPs in ALK, all in linkage disequilibrium, that are associated with a low LR to ethanol in at least one of two behavioral measures, subjective high assessment and body sway, suggesting that ALK expression or function may be involved in the LR to ethanol and future development of AUDs. Only one of these SNPs, rs1881421, results in an amino acid change (Asp 1529 to Glu)
