Circadian rhythm shifts and alcohol access in adolescence synergistically increase alcohol preference and intake in adulthood in male C57BL/6 mice

Adolescents have a natural tendency to be night owls, maintaining delayed circadian rhythms, and this rhythm is in direct conflict with the early wake times required during the school year. This leads to 'social jetlag', chronic circadian stress or desynchrony (CD) in which the rhythm of the intrinsic body clock is out of sync with behavior. CD increases alcohol intake in adolescents and adults, yet it is unknown whether adolescent CD also increases long-term addiction risk. The goal of this study was to determine whether adolescent alcohol intake in CD would increase adult alcohol preference and intake in male C57BL/6 J mice.We measured free access alcohol intake, water intake, and wheel-running activity during a normal 12 h (h) baseline photoperiod and then during shifting lighting schedules (Experiment 1) or a shortened circadian day (Experiment 2).In Experiment 1, altered lighting produced a persistent increase in adolescent alcohol intake and in binge-like drinking (drinking at least 5 licks per minute, with no more than a 1 min break in drinking) in adulthood, but only a transient increase in total alcohol intake for the first week after alcohol was reintroduced in adulthood. In Experiment 2, the circadian shift produced a significant increase in alcohol intake in both adolescence and adulthood. Molecular analysis demonstrated changes in plasma corticosterone and neuronal markers of stress and addiction at the conclusion of these experiments in the CD and alcohol-exposed groups.Thus, we conclude that circadian stress during adolescence is sufficient to produce a long-lasting susceptibility to alcohol use.