Abstract

Disrupted clock gene expression, either in the central clockwork or in peripheral brain areas, is known to affect behavior. Given the comorbidity between affective disorders and alcohol use disorder in males and females, understanding the role of clock genes is necessary to improve drug treatments. The function of clock genes within striatal medium spiny neurons has gained attention for its region-specific associations with neuropsychiatric disorders. Until now, how core clock genes within specific subdivisions of the striatum affect mood and addiction disorders in male and female mice is not fully understood. We measured anxiety-like and depressive-like behaviors as well as ethanol consumption in male and female mice with nucleus accumbens deletion of Bmal1 or Per2. Whereas deletion of Bmal1 in the ventral striatum had minor effects on mood-related behavior, it had significant positive effects on ethanol drinking in both males and females, suggesting that Bmal1 in the nucleus accumbens normally suppresses alcohol consumption independent of sex. Deletion of Per2 augmented alcohol consumption in males, mimicking the effect of Bmal1 nucleus accumbens knockout. The same deletion had no effect in females, pointing to female-specific dissociation between the effect of nucleus accumbens Bmal1 and Per2 on alcohol intake. This study provides new insight into the role of clock genes in the nucleus accumbens in the control of alcohol drinking behavior in male and female mice. Furthermore, lack of effect of Bmal1 and Per2 deletion on mood related behaviors in these mice suggests that the effect on alcohol consumption is direct and not due to changes in mood state.