Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
38583687
DOI
10.1016/j.phrs.2024.107176
PII: S1043-6618(24)00120-8
Knihovny.cz E-resources
- Keywords
- Cannabidiol, Cognitive performance, Fatty acid amide hydrolase, Fragile X syndrome, GPR55 receptors,
- MeSH
- CA1 Region, Hippocampal drug effects metabolism MeSH
- Hippocampus * drug effects metabolism MeSH
- Cannabidiol * pharmacology therapeutic use MeSH
- Rats MeSH
- Disease Models, Animal * MeSH
- Memory drug effects MeSH
- Fragile X Mental Retardation Protein metabolism genetics MeSH
- Receptors, Cannabinoid * metabolism MeSH
- Receptors, G-Protein-Coupled metabolism MeSH
- Recognition, Psychology * drug effects MeSH
- Molecular Docking Simulation MeSH
- Fragile X Syndrome * drug therapy metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fmr1 protein, rat MeSH Browser
- GPR55 protein, rat MeSH Browser
- Cannabidiol * MeSH
- Fragile X Mental Retardation Protein MeSH
- Receptors, Cannabinoid * MeSH
- Receptors, G-Protein-Coupled MeSH
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-Δexon 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-Δexon 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-Δexon 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.
Bone Physiopathology Research Unit Bambino Gesù Children's Hospital IRCCS Rome Italy
Confocal Microscopy Core Facility Bambino Gesù Children's Hospital IRCCS Rome Italy
Dept Biomedical and Biotechnological Sciences University of Catania Catania Italy
Dept Science Roma Tre University Rome Italy
Histology Core Facility Bambino Gesù Children's Hospital IRCCS Rome Italy
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