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A time-dependent contribution of hippocampal CB1 , CB2 and PPARγ receptors to cannabidiol-induced disruption of fear memory consolidation.
Raymundi, Ana Maria; da Silva, Thiago R; Zampronio, Aleksander R; Guimarães, Francisco S; Bertoglio, Leandro J; Stern, Cristina A J.
Afiliação
  • Raymundi AM; Department of Pharmacology, Federal University of Parana, Curitiba, Brazil.
  • da Silva TR; Department of Pharmacology, Federal University of Parana, Curitiba, Brazil.
  • Zampronio AR; Department of Pharmacology, Federal University of Parana, Curitiba, Brazil.
  • Guimarães FS; Department of Pharmacology, University of São Paulo, Ribeirao Preto, Brazil.
  • Bertoglio LJ; Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, Brazil.
  • Stern CAJ; Department of Pharmacology, Federal University of Parana, Curitiba, Brazil.
Br J Pharmacol ; 177(4): 945-957, 2020 02.
Article em En | MEDLINE | ID: mdl-31648363
BACKGROUND AND PURPOSE: In preclinical studies, cannabidiol (CBD) mitigates fear memories by facilitating their extinction or interfering with their generalization and reconsolidation. The brain regions and mechanisms underlying these effects, and their temporal window, are still poorly understood. Here, we have investigated related questions in the dorsal hippocampus (DH) during contextual fear consolidation. EXPERIMENTAL APPROACH: Adult male Wistar rats received CBD (10-30 pmol) intra-DH immediately, 1 or 3 hr after fear conditioning. Effects of CBD on consolidation were inferred behaviourally and by analysing expression of the activity-regulated, cytoskeleton-associated (Arc) protein. The contribution of anandamide, CB1 , CB2 , 5-HT1A , A2A , and PPARγ receptors was also assessed. KEY RESULTS: CBD impaired memory consolidation when given immediately or 1 hr after fear conditioning, but not after 3 hr. Expression of Arc protein in DH was reduced by systemic CBD treatment in both cases. Immediately after fear conditioning, CBD effects were abolished by CB1 or CB2 receptor blockade, partly reduced by 5-HT1A or A2A antagonism, and remained unchanged after antagonism of PPARγ receptors. One hour after fear conditioning, CBD effects were prevented only by PPARγ receptor antagonism. Also, inhibition of fatty acid amide hydrolase by URB597, impaired memory consolidation when infused immediately, but not 1 hr after fear conditioning. CONCLUSIONS AND IMPLICATIONS: CBD disrupts memory consolidation up to 1 hr after fear conditioning, allowing an extended window of opportunity to mitigate aversive memories after their acquisition. Our results suggest time-dependent participation of anandamide, CB1 , CB2 and PPARγ receptors in the DH, during this process.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canabidiol / Consolidação da Memória Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
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: Canabidiol / Consolidação da Memória Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido