In addition to the Tas1r3 gene, rodents have other genetic loci with pleiotropic effects on ethanol and sweetener intake.[194,195] To study T1R-independent mechanisms of association between ethanol and sweetener preferences, we used mice selectively bred for high and low saccharin intake, which have identical allele of the Tas1r3 gene.[55,137] Mice selected for high saccharin intake had higher ethanol intakes and preferences than mice selected for low saccharin intake. Because these mice do not differ in peripheral taste input, we hypothesized that effects on sweetener and ethanol preference are mediated by the central mechanisms. Consistent with this, mice from the two strains differed in number of urocortin 1-containing cells in the brain Edinger–Westphal nucleus, which is involved in the regulation of ethanol consumption.[196] These differences are consistent with the involvement of central mechanisms in selection for sweetener intake and in correlated divergence in ethanol consumption. Therefore, this study has shown that genetic association between consumption of ethanol and sweeteners depends not only on the Tas1r3 locus, but also on at least one other locus, which is involved in central mechanisms regulating ethanol and sweetener intake.
