Selective breeding for ethanol-related traits alters circadian phenotype

Previous studies in mice and rats have shown that selective breeding for high and low ethanol preference results in divergence of circadian phenotype in the selected lines. These results indicate that some alleles influencing ethanol preference also contribute to circadian rhythm regulation. Selective breeding has also been used to produce lines of mice differing in a number of other ethanol-related traits, while studies of phenotypic and genetic correlation indicate that diverse ethanol-related traits are influenced by both shared and unshared genetics. In the present study, we examined several features of circadian activity rhythms in a mouse line selected for binge-like drinking and in mouse lines selected for high and low severity of ethanol withdrawal convulsions. Specifically, Experiment 1 compared High Drinking in the Dark (HDID-1) mice to their genetically heterogeneous progenitor line (HS/Npt), and Experiment 2 compared Withdrawal Seizure-Prone (WSP-2) and Withdrawal Seizure-Resistant (WSR-2) mice. Both line pairs displayed differences in their daily activity patterns under light-dark conditions. In addition, HDID-1 mice showed shorter free-running periods in constant light and less coherent activity rhythms across lighting conditions relative to HS/Npt controls, while WSP-2 mice showed longer free-running periods in constant darkness relative to WSR-2 mice. These results strengthen the evidence for genetic linkages between responsiveness to ethanol and circadian regulation, and extend this evidence to include ethanol-related phenotypes other than preference drinking. However, the present results also indicate that the nature of genetic correlations between and within phenotypic domains is highly complex.