Table of Contents
ISRN Pharmacology
Volume 2012, Article ID 276902, 10 pages
Research Article

Neural Circuit in the Dorsal Raphe Nucleus Responsible for Cannabinoid-Mediated Increases in 5-HT Efflux in the Nucleus Accumbens of the Rat Brain

Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA

Received 5 April 2012; Accepted 29 May 2012

Academic Editors: G. A. Gudelsky and D. K. Miller

Copyright © 2012 Rui Tao and Zhiyuan Ma. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In vivo microdialysis was used in this study to reveal the role of cannabinoids in regulating serotonin (5-HT) efflux in the nucleus accumbens (NAcc) and dorsal raphe nucleus (DRN). The cannabinoid CB1 receptor agonists WIN55212-2 and CP55940 systematically administered to rats caused significant increases in 5-HT efflux in the NAcc but failed to have an effect in the DRN. To reveal mechanisms underlying regionally selective responses, we tested the hypothesis that cannabinoids have both direct and indirect effects on 5-HT efflux, depending on the location of CB1 receptors in the neural circuit between DRN and NAcc. We showed that the direct effect of cannabinoids caused a reduction in 5-HT efflux whereas the indirect effect resulted in an increase. Furthermore, the indirect effect was blocked by the GABAA receptor antagonist bicuculline in the DRN, suggesting that the action is likely due to a presynaptic inhibition on GABAergic activity that exerts a tonic influence on neuronal circuits regulating 5-HT efflux. Involvement of GABAergic neurons was confirmed by measuring changes in GABA efflux. Taken together, our study suggests that cannabinoids may have direct and indirect effects on the 5-HT regulatory circuits, resulting in regionally selective changes of 5-HT efflux in the brain.