Since Alk expression in the striatum is negatively correlated with ethanol intake across the BXD RI strains (Figure 3B), we hypothesized that AlkKO mice would consume more ethanol than control mice. We tested ethanol intake in a limited intermittent-access drinking in the dark paradigm adapted from Rhodes et al. [30], in which mice drink to intoxication. Male wild-type and homozygous AlkKO mice were examined for consumption of a 20% ethanol solution over a 4-hour period 3 times per week during the dark cycle, for a total of 8 sessions. We observed a significant effect of genotype and drinking session, but no genotype by session interaction. This analysis indicates that all mice escalated their intake of ethanol after repeated sessions and that AlkKO mice consumed more ethanol overall than wild-type controls under these conditions (Figure 5A). Heterozygous male AlkKO mice were also tested and did not show a significant difference in ethanol intake when compared to wild-type controls (data not shown). An advantage of testing mice in the dark phase under limited access conditions is that mice will drink to intoxication.
