Alegre Zurano, LaiaCáceres-Rodriguez, AlbaBerbegal-Sáez, PaulaLassalle, OlivierManzoni, OlivierValverde Granados, Olga2023-12-052023-12-052023Alegre-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/s41598-023-45476-72045-2322http://hdl.handle.net/10230/58441A 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.application/pdfeng© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-023-45476-7MotivationRewardSynaptic plasticityinfo:eu-repo/semantics/openAccess