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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Psychopharmacology; v. 236, n. 6, p. 1863-1874, JUN 2019.
• Web of Science Citations: 2

Abstract

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)

• FAPESP's process: 17/11855-8 - Study of corpus striatum and ventral mesencephalon endocanabinoid influence on neostriato-nigro-tectal GABAergic pathways during panic reactions of rodents threatened by venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/22647-7 - Study of glutamatergic pathways from the medial amygdala on ventromedial hypothalamus endocannabinoid signalling during the defensive behaviour elicited by mice threatened by venomous snakes
• Grantee: Tayllon dos Anjos Garcia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants