Opposing roles of dorsomedial hypothalamic CB1 and TRPV1 receptors in anandamide signaling during the panic-like response elicited in mice by Brazilian rainbow Boidae snakes

Autor(es)

dos Anjos-Garcia, Taylion ^{[1, 2, 3]} ; Coimbra, Norberto Cysne ^{[4, 1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, FMRP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, NAP USP Neurobiol Emot Res Ctr NuPNE, Ribeirao Preto Med Sch, FMRP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ophidiarium LNN FMRP USP INeC, Ribeirao Preto Sch Med, FMRP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Behav Neurosci Inst INeC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Psychopharmacology; v. 236, n. 6, p. 1863-1874, JUN 2019.
• Citações Web of Science: 2

Resumo

RationaleThe endocannabinoid system plays an important role in the organization of panic-like defensive behavior. Threatening situations stimulate brain areas, such as the dorsomedial hypothalamus (DMH). However, there is a lack of studies addressing the role of the DMH endocannabinoid system in panic-like responses.ObjectivesWe aimed to verify which mechanisms underlie anandamide-mediated responses in the DMH.MethodsTo test the hypothesis that the anandamide produces panicolytic-like effects, we treated mice with intra-DMH microinjections of vehicle or increasing doses of anandamide (0.5, 5, or 50pmol) and then performed confrontation with the South American snake Epicrates cenchria assisi.ResultsIntra-DMH anandamide treatment yielded a U-shaped dose-response curve with no effect of the lowest (0.5pmol) or the highest (50pmol) dose and significant inhibition of panic-like responses at the intermediate (5pmol) dose. In addition, this panicolytic-like effect was prevented by pretreatment of the DMH with the CB1 receptor antagonist AM251 (100pmol). However, pretreatment of the DMH with the TRPV1 receptor antagonist 6-iodo-nordihydrocapsaicin (3nmol) restored the panicolytic-like effect of the highest dose of anandamide. Immunohistochemistry revealed that CB1 receptors were present primarily on axonal fibers, while TRPV1 receptors were found almost exclusively surrounding the perikarya in DMH.ConclusionsThe present results suggest that anandamide exerts a panicolytic-like effect in the DMH by activation of CB1 receptors and that TRPV1 receptors are related to the lack of effect of the highest dose of anandamide. (AU)

• Processo FAPESP: 17/11855-8 - Estudo da influência de endocanabinoides do corpo estriado e do mesencéfalo ventral na atividade das projeções GABAérgicas neoestriado-nigro-tectais durante as reações de pânico de roedores ameaçados por serpentes peçonhentas
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/22647-7 - Estudo das vias glutamatérgicas do núcleo medial do complexo amigdaloide na modulação endocanabinoide do hipotálamo ventromedial no comportamento de defesa de camundongos ameaçados por serpentes peçonhentas
• Beneficiário: Tayllon dos Anjos Garcia
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/03798-0 - Envolvimento de receptores opióides e endocanabinóides da substância negra na modulação da atividade da via GABAérgica nigro-tectal durante a organização do comportamento de defesa eliciado por roedores confrontados com serpentes veneníferas
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular