Bmal1 in the striatum influences alcohol intake in a sexually dimorphic manner

In order to examine the role of the circadian clock driver Brain and Muscle ARNT-Like 1 (Bmal1) in alcohol consumption, de Zavalia et al assess the effects of (Bmal1) deletion in the mouse striatum on alcohol drinking behavior. They show that striatal Bmal1 and downstream effects on Period Circadian Regulator 2 (Per2) play a sex-dependent role on alcohol consumption propensity. Alcohol consumption has been strongly associated with circadian clock gene expression in mammals. Analysis of clock genes revealed a potential role of Bmal1 in the control of alcohol drinking behavior. However, a causal role of Bmal1 and neural pathways through which it may influence alcohol intake have not yet been established. Here we show that selective ablation of Bmal1 (Cre/loxP system) from medium spiny neurons of the striatum induces sexual dimorphic alterations in alcohol consumption in mice, resulting in augmentation of voluntary alcohol intake in males and repression of intake in females. Per2mRNA expression, quantified by qPCR, decreases in the striatum after the deletion of Bmal1. To address the possibility that the effect of striatal Bmal1 deletion on alcohol intake and preference involves changes in the local expression of Per2, voluntary alcohol intake (two-bottle, free-choice paradigm) was studied in mice with a selective ablation of Per2 from medium spiny neurons of the striatum. Striatal ablation of Per2 increases voluntary alcohol intake in males but has no effect in females. Striatal Bmal1 and Per2 expression thus may contribute to the propensity to consume alcohol in a sex -specific manner in mice.

Automated summary

The study reveals that the expression levels of Bmal1 and Per2 in the mouse striatum may have a gender-dependent impact on alcohol consumption propensity, with deletion of Bmal1 resulting in increased alcohol intake in males and decreased intake in females.