Endocannabinoid signaling and the regulation of the serotonin system

Endogenous cannabinoids, also called endocannabinoids (eCBs), are lipid signaling molecules in the mammalians' central nervous system (CNS), where they regulate neuronal functions and behaviors by activating cannabinoid receptors. The ubiquitous distribution of eCBs in neuronal populations that are associated with stress responses, such as dorsal raphe nucleus (DRn) serotonin (5-HT) neurons suggests that eCB signaling plays a central role in the regulation of stress-related behaviors. Consistent with this notion, human and animal studies have established that eCB signaling is a key modulator of emotional homeostasis and that a dysfunction of eCB signaling contributes to stress-related psychiatric disorders, including anxiety and depression. This leads to the current view that the eCB signaling could be an excellent target for the development of novel therapeutic intervention for stress-related mood disorders. Over the past few years, extensive research has focused on the functional interaction between eCB signaling and 5-HT systems. As a result, steady progress is made in our understanding of the cellular mechanisms by which eCB signaling regulates the function of 5-HT system. In this chapter, we review the most recent advances in our understanding of the cellular mechanisms by which eCBs modulate the function of the 5-HT system and how stress mediators regulate eCB signaling in the DRn.