Because Lightweight animals exhibited dramatically altered responses to acute ethanol injection, we assayed free choice ethanol preference and consumption using a two bottle choice test. On both a B6 and a B6D2 F1 hybrid background, Lightweight heterozygotes displayed a higher preference for and consumption of ethanol than wild-type littermates. However, on a B6D2 F1 background, in addition to having a higher preference for and consumption of ethanol (at 6% and 10%), Lightweight animals also consume more water than wild-type littermates, and when offered water or water plus a tastant (saccharin), they tend to choose the bottle containing the tastant over water alone. Given these observations, in combination with the body composition and food consumption analysis performed in B6 Lightweight animals, we favor a conservative interpretation of the two bottle choice data: Lightweight animals have a higher preference for and consumption of ethanol; however, we cannot exclude the possibility that taste preference and/or alterations in metabolism could contribute to this phenotype. Because the unc-79 protein is widely expressed throughout the central nervous system, tissue-specific deletion using conditional mutagenesis or RNA interference may yield more specific results. Nonetheless, it is clear that Lightweight heterozygotes voluntarily consume more ethanol than wild-type littermates.
