A time-dependent contribution of hippocampal CB1, CB2, and PPARγ receptors to cannabidiol-induced disruption of worry memory consolidation.

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BACKGROUND AND Objective:

Preclinical research have shown that cannabidiol (CBD) mitigates worry 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 nonetheless poorly understood. The present paper aimed at investigating associated inquiries in the dorsal hippocampus (DH) in the course of contextual worry consolidation.

EXPERIMENTAL Strategy:

Adult male Wistar rats received CBD (10-30 pmol) intra-DH instantly, 1 or three h soon after worry conditioning. The CBD-induced effects on consolidation had been inferred behaviorally and by the evaluation of the activity-regulated cytoskeleton-related (Arc) protein expression. The relative contribution of anandamide, CB1, CB2, five-HT1A , A2A , and PPARγ receptors was also examined.

Important Final results:

CBD impaired memory consolidation when offered instantly or 1 h soon after worry conditioning, but not soon after three h. The DH Arc expression was lowered by systemic CBD therapy in each situations. Instantly soon after worry conditioning, the CBD impact was abolished by CB1 or CB2 receptor blockade, partly lowered by five-HT1A or A2A antagonism, and remained unchanged soon after antagonism of PPARγ receptors. 1 h soon after worry conditioning, the CBD impact was only prevented by PPARγ receptor antagonism. In addition to, the FAAH inhibition impaired memory consolidation when URB597 was infused instantly, but not 1 hour soon after worry conditioning.

CONCLUSIONS AND IMPLICATIONS:

CBD disrupts memory consolidation up to 1 h soon after worry conditioning, enabling an extended window of chance to mitigate aversive memories soon after their acquisition. The final results recommend time-dependent participation of DH anandamide, CB1, CB2, and PPARγ receptors in this method.

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