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• Exposure to a disrupted light–dark cycle alters mood-related behaviors in mice. • Clock genes are abundantly expressed in the prefrontal cortex of mice. • Circadian disorganization alters rhythmic expression of clock and immediate early genes in the prefrontal cortex of mice. • The prefrontal cortex may play an important role in the integration of mood and the circadian clock. Disturbance of the daily cycles in sleep and wakefulness induced by conditions such as shift work and jet lag can increase the risk of affective disorders including anxiety and depression. The way such circadian disorganization disrupts the regulation of mood, however, is not well understood. More specifically, the impact of circadian disorganization on the daily rhythms of the neuronal function that controls mood remains unclear. We therefore investigated the effects of circadian disorganization on expression rhythms of clock genes as well as immediate early genes (IEGs) in several mood-controlling regions of the brain. To introduce circadian disorganization of behaviors, we exposed male C57BL/6J mice to chronic reversal of the light–dark cycle and we found a marked negative mood phenotype in these mice. Importantly, the most adverse effect of circadian disorganization on expression rhythms of clock and IEGs was observed in the prefrontal cortex (PFC) when compared to that in other mood-related areas of the brain. Dysregulation of molecular rhythms in the PFC is therefore suggested to be associated with the development of mood disorders in conditions including shift work and jet lag. [ABSTRACT FROM AUTHOR]

• Rev-erbα knockout mice exhibit both positive and negative mood phenotypes. • Rev-erbα deficiency leads to dysregulation of the dopaminergic and serotonergic systems. • The Rev-erbα gene is required for the regulation of genes essential for neurogenesis in the murine prefrontal cortex. Mood disorders such as depression, anxiety, and bipolar disorder are highly associated with disrupted daily rhythms of activity, which are often observed in shift work and sleep disturbance in humans. Recent studies have proposed the REV-ERBα protein as a key circadian nuclear receptor that links behavioural rhythms to mood regulation. However, how the Rev-erbα gene participates in the regulation of mood remains poorly understood. Here, we show that the regulation of the serotonergic (5-HTergic) system, which plays a central role in stress-induced mood behaviours, is markedly disrupted in Rev-erbα−/− mice. Rev-erbα−/− mice exhibit both negative and positive behavioural phenotypes, including anxiety-like and mania-like behaviours, when subjected to a stressful environment. Importantly, Rev-erbα−/− mice show a significant decrease in the expression of a gene that encodes the rate-limiting enzyme of serotonin (5-HT) synthesis in the raphe nuclei (RN). In addition, 5-HT levels in Rev-erbα−/− mice are significantly reduced in the prefrontal cortex, which receives strong inputs from the RN and controls stress-related behaviours. Our findings indicate that Rev-erbα plays an important role in controlling the 5-HTergic system and thus regulates mood and behaviour. [ABSTRACT FROM AUTHOR]