Stress and Endocannabinoids in Serotonin Neurons

Dr. Haj-Dahmane investigated the role of the endocannabinoid (eCB) system in regulation of stress responses and anxiety-related behaviors which play a role in addicted behaviors. The long-term objective of this research is to delineate the cellular and molecular mechanisms by which stress modulates eCB signaling in dorsal raphe (DR) serotonergic (5-HT) neurons. A combination of electrophysiological, pharmacological and neurochemical approaches was used to 1) test the hypothesis that glucocorticoids acutely enhance eCB systhesis/release in DR 5-HT neurons, 2) elucidate the signal transduction mechanisms by which glucocorticoids enhance eCB signaling in DR 5-HT neurons, 3) determine the mechanisms of severe stress-induced down-regulation of eCB signaling in DR 5-HT neurons. Given the role of 5-HT and eCB systems in the regulation of stress-related behaviors, the results from the proposed research should improve understanding of the etiology of anxiety disorder and may contribute to the development of more effective anxiolytics (anti-anxiety medications). Co-investigator on the study is Dr. Troy Wood, UB’s Department of Chemistry. Funded by a grant of $1,688,468 from NIMH, 2007-2012.