Rationale: Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood. Objective: The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD. Methods: Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG. Results: The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist. Conclusions: Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG. © 2012 Springer-Verlag Berlin Heidelberg.
CITATION STYLE
Campos, A. C., De Paula Soares, V., Carvalho, M. C., Ferreira, F. R., Vicente, M. A., Brandão, M. L., … Guimarães, F. S. (2013). Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology, 226(1), 13–24. https://doi.org/10.1007/s00213-012-2878-7
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