Genetic correlations among ethanol-related behaviors and neurotensin receptors in long sleep (LS) x short sleep (SS) recombinant inbred strains of mice.

Abstract

Studies were designed to examine the hypothesis that genetic based differences in sensitivity to several behavioral effects of ethanol are mediated, in part, by shared genes and that some of ethanol's actions are mediated by brain neurotensinergic processes. In these studies we have used recombinant inbred (RI) strains of mice derived from Long Sleep (LS/Ibg) and Short Sleep (SS/Ibg) lines of mice. The LS and SS mice were selectively bred to differ in hypnotic sensitivity but also differ in hypothermia and locomotor effects of ethanol. Therefore LS x SS RI strains were used to answer the question whether there are shared genetic influences on these diverse ethanol actions. Moreover, since the LS and SS mice were found to differ in neurotensin (NT) receptor densities in various brain regions, the LS x SS RI strains were used to determine associations between NT receptor densities and ethanol actions. The results showed a significant genetic correlation (r = .38) between hypnotic sensitivity and low-dose locomotor effects of ethanol and indicated multigenetic influences, with estimates of seven, four and three genes being responsible for mediating differences in hypnotic, hypothermic, and locomotor effects of ethanol, respectively. The findings are consistent with one or more genes having pleiotropic effects on these ethanol actions.