Our work suggests that Per3, a circadian regulator, has a pleiotropic influence on response to alcohol and stress, and provides a potential causal link between stress, sleep disruption and addiction. Expression of Per3 varies up to fivefold among strains of mice and is under strong cis-acting control in the BXD family. In addition to these prominent genotypic effects on expression, there are also effects caused by alcohol and an interaction with restraint-induced stress. Our study is the first to attempt to systematically investigate the association between Per3 and behavioral phenotypes. The implication of our study is that Per3 serves as a new candidate gene for alcohol- and stress-responsive behavior, and supports a role for Per3 in circadian clock function.45
