Mood disorders, like Major Depressive Disorder (MDD) and Bipolar Disorder (BD), are associated with circadian rhythm disruptions, but the causal relationship between the two is not well understood. Previous data from our lab show an association between depression-like helpless behavior in mice and loss of circadian rhythms in mood- regulating brain areas, including the nucleus accumbens (NAc) and the periaqueductal grey (PAG). These results led to the hypothesis that reduced circadian rhythm amplitude in mood-regulating brain areas contributes to the development of depression-like behaviors in mice, as tested by knockdown of an essential clock gene and several behavioral tests, including sucrose preference, open field test, tail suspension test, and learned helplessness. In addition, it is known that the PAG serotonin receptors (5HTR) play a critical role in developing helpless behavior. Hence, we hypothesized that circadian rhythms regulate 5HTR expression in the PAG and are involved in mood regulation. Our results indicate that losing rhythms in single mood-regulating brain regions is not sufficient for development of depression-like behavior in mice. However, disturbing rhythms throughout the entire brain by disrupting the central circadian pacemaker in the suprachiasmatic nucleus (SCN) leads to depression-like behavior in learned helplessness and significant differences in the open field test. These results suggest that disturbed circadian clocks may lead to the development of mood disorders and represent a starting point for other research to explain how circadian rhythm disruptions relate to mood disorders in psychiatric patients