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A time‐dependent contribution of hippocampal CB 1 , CB 2 and PPARγ receptors to cannabidiol‐induced disruption of fear memory consolidation
Author(s) -
Raymundi Ana Maria,
Silva Thiago R.,
Zampronio Aleksander R.,
Guimarães Francisco S.,
Bertoglio Leandro J.,
Stern Cristina A.J.
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14895
Subject(s) - memory consolidation , cannabinoid receptor , cannabidiol , endocannabinoid system , neuroscience , fear conditioning , hippocampal formation , receptor , cannabinoid , psychology , pharmacology , chemistry , hippocampus , medicine , endocrinology , antagonist , amygdala , cannabis , psychiatry
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, CB 1 , CB 2 , 5‐HT 1A , A 2A , 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 CB 1 or CB 2 receptor blockade, partly reduced by 5‐HT 1A or A 2A 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, CB 1 , CB 2 and PPARγ receptors in the DH, during this process.