Endocannabinoid Signaling and the Regulation of the Serotonin System

  • Samir Haj-DahmaneEmail author
  • Roh-Yu Shen


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.


Dorsal raphe Endocannabinoid Serotonin CB1 receptors Glutamate Stress Glucocorticoids 





5-hydroxytryptamine (serotonin)


dorsal raphe nucleus


diacyl-glycerol lipase


cyclooxygenase type 2


monoglyceride lipases


fatty acid amid hydrolase


excitatory postsynaptic current

WIN 55,212-2

R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolol[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate


depolarization-induced suppression of excitation


paired-pulse ratio


coefficient of variation


long-term depression

JZL 184

4-[Bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxyl acid 4-nitrophenyl ester

PF 750




Work in the Author’s lab was supported by research grants from the National Institutes of Health research grant MH 078009 to S. HD and AA12435 to R-Y. S.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Research Institute on AddictionsUniversity at Buffalo, State University of New YorkBuffaloUSA

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