Your browser doesn't support javascript.
loading
Opposing roles for cannabinoid receptor type-1 (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats.
Casarotto, Plínio C; Terzian, Ana Luisa B; Aguiar, Daniele C; Zangrossi, Hélio; Guimarães, Francisco S; Wotjak, Carsten T; Moreira, Fabrício A.
Afiliação
  • Casarotto PC; Department of Pharmacology, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Neuropsychopharmacology ; 37(2): 478-86, 2012 Jan.
Article em En | MEDLINE | ID: mdl-21937980
The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety- and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pânico / Receptor CB1 de Canabinoide / Canais de Cátion TRPV Limite: Animals Idioma: En Revista: Neuropsychopharmacology Assunto da revista: NEUROLOGIA / PSICOFARMACOLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pânico / Receptor CB1 de Canabinoide / Canais de Cátion TRPV Limite: Animals Idioma: En Revista: Neuropsychopharmacology Assunto da revista: NEUROLOGIA / PSICOFARMACOLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido