Dorsolateral periaqueductal gray matter CB1 and TRPV1 receptors exert opposite modulation on expression of contextual fear conditioning

• Published in: Neuropharmacology Vol. 103; pp. 257 - 269
• Main Authors: Uliana, D.L., Hott, S.C., Lisboa, S.F., Resstel, L.B.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2016
• Subjects: Animals; Capsaicin - administration & dosage; CB1; Conditioned emotional response; Conditioning, Classical - physiology; contextual fear conditioning; Dorsolateral periaqueductal gray; Fear - physiology; Male; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - physiology; NMDA receptor; Periaqueductal Gray - physiology; Piperidines - administration & dosage; Pyrazoles - administration & dosage; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Signal Transduction; Soluble Guanylyl Cyclase - antagonists & inhibitors; Soluble Guanylyl Cyclase - physiology; TRPV Cation Channels - agonists; TRPV Cation Channels - physiology; TRPV1; Dorsolateral periaqueductal gray; Conditioned emotional response; CB1; Nitric oxide; contextual fear conditioning; TRPV1; NMDA receptor
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2015.12.020

Cannabinoid type 1 (CB1) and Transient Potential Vanilloid type 1 (TRPV1) receptors in the dorsolateral periaqueductal gray (dlPAG) matter are involved in the modulation of conditioned response. Both CB1 and TRPV1 receptors are related to glutamate release and nitric oxide (NO) synthesis. It was previously demonstrated that both NMDA glutamate receptors and NO are involved in the conditioned emotional response. Therefore, one aim of this work was to verify whether dlPAG CB1 and TRPV1 receptors modulate the expression of contextual conditioned emotional response. Moreover, we also investigated the involvement of NMDA receptors and the NO pathway in this response. Male Wistar rats with local dlPAG guide cannula were submitted to contextual fear conditioning. Following 24 h, a polyethylene catheter was implanted in the femoral artery for cardiovascular recordings. After an additional 24 h, drugs were administered in the dlPAG and freezing behavior and autonomic responses were recorded during chamber re-exposure. Both a CB1 antagonist (AM251) and a TRPV1 agonist (Capsaicin; CPS) increased the expression of a conditioned emotional response. This response was prevented by an NMDA antagonist, a preferential neuronal NO synthase inhibitor, an NO scavenger and a soluble guanylate cyclase inhibitor (sGC). Furthermore, pretreatment with a TRPV1 antagonist also prevented the increased conditioned emotional response induced by AM251. Considering that GABA can counterbalance glutamate effects, we also investigated whether GABAA receptors were involved in the effect of a higher dose of AM251. Pretreatment with a GABAA receptor antagonist caused an increased conditioned emotional response by AM251. Our results support the possibility that dlPAG CB1 and TRPV1 receptors are involved in the expression of conditioned emotional response through the NMDA/NO/sGC pathway. Moreover, the opposite effects exerted by GABA and glutamate could produce different outcomes of drugs modulating eCBs. •CB1 and TRPV1 are related with the expression of conditioned response.•NMDA/NO/cGMP pathway participate in CB1 and TRPV1 effects of conditioned response.•CB1 and TRPV1 interact in the modulation of conditioned response.•GABAA receptor is involved in lack of effect at the higher dose of CB1 antagonist.