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Fig. 2. (A) Pharmacological REV-ERBα activity inhibition by microinfusion of SR8278 into the ventral midbrain (VMB) of wild type (WT) mice induced mania-like behaviors, such as decreased depression-and anxiety-like phenotypes at dusk (circadian time 12 h [CT12]) with disappearance of daily variation of mood-related behaviors in the tail suspension test (TST) and elevated plus maze test (EPM) (). 6-OHDA-treated mice exhibited disruption of daily rhythmic mood-related behaviors toward increased depression- and anxiety-like behaviors at dawn (CT00) in the TST and EPM (unpublished data). **p < 0.01, CT00 vs. CT12; ††p < 0.01, VEH vs. SR8278. (B) Microinfusion of SR8278 into the VMB induced a hyperdopaminergic state without daily oscillation of DA, which was caused by loss of the repressive function of REV-ERBα on TH expression. Conversely, 6-OHDA-treated mice showed a hypodopaminergic state owing to DAergic neuronal death in the SNpc. Hyperdopaminergic and hypodopaminergic states can induce mood dysfunction. Therefore, appropriate levels of DA with circadian oscillation may be important to sustain circadian mood-related behaviors.
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