Sex-Dependent Effects of Circadian Rhythm Disruptions on Novel Object Recognition Memory, Locomotion, Pain Threshold, Rearing Behavior, and BDNF and GSK-3β Hippocampal Levels in Rats.

Evidence has shown that constant light or constant darkness significantly impairs cognitive functions and affects the mood state. The present study investigated the effect of circadian rhythm disturbances (circadian rhythm disruptions, CRDs) on locomotor activity, rearing behavior, pain threshold, novel object recognition memory, and brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 beta (GSK-3β) expression levels in the hippocampus of both sexes of rats. CRD was done using a combination of constant light (48 h) and constant darkness (48 h) periods for 8 (short-term), 16 (midterm), or 24 (long-term) days. The results showed CRD in all protocols increased locomotor activity in males, whereas in females, only long-term CRD increased it. Long-term CRD increased rearing only in females, whereas in males, only midterm CRD decreased rearing. Short- and midterm CRD in males decreased pain threshold, whereas in females, only midterm CRD decreased pain threshold. Novel object recognition memory was impaired in both sexes following all protocols of CRD. All protocols of CRD in females downregulated BDNF, whereas in males, short-term CRD had no effect. GSK-3β was increased following long-term CRD in both sexes. Spearman correlation test showed that BDNF function may be associated with changes in some behavioral functions in both sexes; however, GSK-3β function may be associated with some behavioral changes only in females. In conclusion, we showed sex differences in the effect of CRD on locomotor activity, rearing behavior, and pain threshold. Also, GSK-3β may show a sex-dependent role in the modulation of behavioral changes induced by CRD.