Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

Alegre Zurano, Laia; Cáceres-Rodriguez, Alba; Berbegal-Sáez, Paula; Lassalle, Olivier; Manzoni, Olivier; Valverde Granados, Olga

doi:http://dx.doi.org/10.1038/s41598-023-45476-7

Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

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Alegre-Zurano L, Caceres-Rodriguez A, Berbegal-Sáez P, Lassalle O, Manzoni O, Valverde O. Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition. Sci Rep. 2023 Oct 25;13(1):18229. DOI: 10.1038/s41598-023-45476-7

Abstract

A single dose of cocaine abolishes endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 h of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit. As previously reported, after a single dose of cocaine (20 mg/kg), mice displayed impaired eCB-LTD in the NAc. Such cocaine-induced neuroplastic impairment was accompanied by an altered preference for saccharin and social interactions and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. The pharmacological increase of anandamide through the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg) reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect saccharin preference. Overall, this research underlines the neuroplastic and behavioral alterations occurring after the initial use of cocaine and suggests a potential role for anandamide.