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N-arachidonoyl-serotonin, a dual FAAH and TRPV1 blocker, inhibits the retrieval of contextual fear memory: Role of the cannabinoid CB1 receptor in the dorsal hippocampus.
Gobira, Pedro H; Lima, Isabel V; Batista, Luara A; de Oliveira, Antônio C; Resstel, Leonardo B; Wotjak, Carsten T; Aguiar, Daniele C; Moreira, Fabricio A.
Afiliação
  • Gobira PH; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Lima IV; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Batista LA; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • de Oliveira AC; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Resstel LB; 2 Department of Pharmacology, Medical School of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
  • Wotjak CT; 3 Max Planck Institute of Psychiatry, Munich, Germany.
  • Aguiar DC; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • Moreira FA; 1 Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
J Psychopharmacol ; 31(6): 750-756, 2017 06.
Article em En | MEDLINE | ID: mdl-28583049
Anandamide, an endocannabinoid, inhibits aversive responses by activating the CB1 cannabinoid receptor. At high concentrations, however, anandamide may exert pro-aversive activities mediated by the transient receptor potential vanilloid type-1 channel (TRPV1). Accordingly, N-arachidonoyl-serotonin (AA-5-HT), a dual blocker of the anandamide-hydrolysing enzyme fatty acid amide hydrolase (FAAH) and the TRPV1 channel, induces anxiolytic-like effects. Here we tested the hypothesis that AA-5-HT inhibits the expression of contextual fear conditioning by facilitating CB1 receptor signalling in the dorsal hippocampus of mice. Intraperitoneal injection of AA-5-HT (0.1, 0.3, 1 mg/kg) inhibited the retrieval of contextual fear memory (freezing response). The effect of AA-5-HT (0.3 mg/kg) was prevented by systemic injection of the CB1 receptor antagonist, AM251 (1.0 mg/kg), and mimicked by simultaneous FAAH inhibition (URB597, 0.3 mg/kg) and TRPV1 blockage (SB366791, 1 mg/kg). Injection of AA-5-HT (0.125, 0.25, 0.5 nmol) into the dorsal hippocampus also reduced freezing. Finally, the effect of systemic AA-5-HT (0.3 mg/kg) was prevented by intra-hippocampal injection of AM251 (1 nmol). In conclusion, dual FAAH and TRPV1 blockage inhibits contextual fear memory by facilitating anandamide-induced CB1 receptor activation in the dorsal hippocampus. This approach may lead to new pharmacological treatments for traumatic memories and related psychiatric disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serotonina / Ácidos Araquidônicos / Receptor CB1 de Canabinoide / Canais de Cátion TRPV / Medo / Amidoidrolases / Hipocampo / Memória Limite: Animals Idioma: En Revista: J Psychopharmacol Assunto da revista: PSICOFARMACOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serotonina / Ácidos Araquidônicos / Receptor CB1 de Canabinoide / Canais de Cátion TRPV / Medo / Amidoidrolases / Hipocampo / Memória Limite: Animals Idioma: En Revista: J Psychopharmacol Assunto da revista: PSICOFARMACOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos