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Transient receptor potential vanilloid type 1 (TRPV1) receptors in the dHIP modulate contextual fear conditioning by triggering a cascade involving glutamate release, nitric oxide (NO) formation and cyclic guanosine monophosphate (cGMP) production. The present study investigated the involvement of dHIP TRPV1 receptors and their interaction with the glutamate\/NO\/cGMP signalling pathway in modulating the expression of contextual fear conditioning (CFC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male Wistar rats were submitted to an aversive contextual conditioning session and, 48\u2009h later, were re\u2010introduced to the same aversive environment where the freezing response and autonomic activity (evidenced by increased arterial pressure and heart rate and a decrease in tail temperature) were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The results demonstrated that the TRPV1 antagonist 6\u2010I\u2010CPS in dHIP reduced the expression of CFC, whereas the agonist capsaicin had the opposite effect. Furthermore, dHIP pre\u2010treatment with an NMDA receptor antagonist (AP7), neuronal NO synthase inhibitor (N\u2010propyl\u2010L\u2010arginine), NO scavenger (c\u2010PTIO) or guanylate cyclase inhibitor (ODQ) attenuated capsaicin\u2010induced increases in CFC. Finally, we observed that re\u2010exposure to the aversive chamber increased dHIP NO levels in conditioned animals compared with a non\u2010conditioned group, which was prevented by the administration of the TRPV1 antagonist, 6\u2010I\u2010CPS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our study revealed that TRPV1 receptors in the dHIP play a crucial role in modulating contextual fear expression by acting through the NMDA receptor\/NO\/cGMP signalling pathway, providing important insights into the underlying mechanisms and potential therapeutic avenues associated with these pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17384","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T12:04:30Z","timestamp":1731499470000},"page":"1107-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The expression of contextual fear conditioning involves the dorsal hippocampus TRPV1 receptor interacting with the NMDA\/NO\/cGMP signalling pathway"],"prefix":"10.1111","volume":"182","author":[{"given":"Gabriela L.","family":"Bertacchini","sequence":"first","affiliation":[{"name":"State University of Mato Grosso do Sul \u2010 Medicine UEMS  Campo Grande Brazil"},{"name":"Department of Pharmacology, Medical School of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreza B.","family":"Sonego","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina F.","family":"Lisboa","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, School of Pharmaceutical Sciences University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi C.","family":"Lagatta","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Food and Nutrition Federal University of Mato Grosso do Sul  Campo Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo B. 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