Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors.

Autor: Manduca A; Dept. Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy; Dept. Science, Roma Tre University, Rome, Italy; Neuroendocrinology, Metabolism and Neuropharmacology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. Electronic address: antonia.manduca@uniroma1.it., Buzzelli V; Dept. Science, Roma Tre University, Rome, Italy., Rava A; Dept. Science, Roma Tre University, Rome, Italy., Feo A; Dept. Science, Roma Tre University, Rome, Italy., Carbone E; Dept. Science, Roma Tre University, Rome, Italy., Schiavi S; Dept. Science, Roma Tre University, Rome, Italy., Peruzzi B; Bone Physiopathology Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., D'Oria V; Confocal Microscopy Core Facility, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Pezzullo M; Histology Core Facility, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Pasquadibisceglie A; Dept. Science, Roma Tre University, Rome, Italy., Polticelli F; Dept. Science, Roma Tre University, Rome, Italy., Micale V; Dept. Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Kuchar M; Forensic Laboratory of Biologically Active Substances, Dept. Chemistry of Natural Compounds, University of Chemistry and Technologies, Prague, Czech Republic; Psychedelic Research Center, National Institute of Mental Health, Klecany, Czech Republic., Trezza V; Dept. Science, Roma Tre University, Rome, Italy; Neuroendocrinology, Metabolism and Neuropharmacology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. Electronic address: viviana.trezza@uniroma3.it.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2024 May; Vol. 203, pp. 107176. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1016/j.phrs.2024.107176
Abstrakt: Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1- Δ exon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1- Δ exon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1- Δ exon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.
Competing Interests: Declaration of Competing Interest I declare on behalf of all authors that we do not have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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