The circadian gene Nr1d1 in the mouse nucleus accumbens modulates social reward and anxiety-related behavior

Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to non-parental adult mice to determine whether decreases in Nr1d1 expression in NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social reward and mood-related behaviors. We also used microarray analysis of to identify gene expression alterations induced by the lowering of Nr1d1 expression. We used microarrays to evalute the effects of knockdown of mRNA for Nr1d1 in nuclues accumbens on gene expression. In total, 23 total RNA samples derived from micropunched nucleus accumbens were used for microarray analysis: For females, there were 5 control and 6 Nr1d1 knockdown samples. For males, there were 6 control and 6 Nr1d1 knockdown samples. All samples are biological replicates.