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Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice

dc.rights.licenseopenen_US
dc.contributor.authorBUSQUETS-GARCIA, Arnau
dc.contributor.authorSORIA-GOMEZ, Edgar
dc.contributor.authorREDON, Bastien
dc.contributor.authorMACKENBACH, Y
dc.contributor.authorVALLEE, Monique
dc.contributor.authorCHAOULOFF, Francis
dc.contributor.authorVARILH, Marjorie
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorFERREIRA, Guillaume
dc.contributor.authorPIAZZA, Pier-Vincenzo
dc.contributor.authorMARSICANO, Giovanni
dc.date.accessioned2021-09-27T10:42:40Z
dc.date.available2021-09-27T10:42:40Z
dc.date.issued2017-11
dc.identifier.issn1359-4184en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112409
dc.description.abstractEnCannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of ?(9)-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS.
dc.description.sponsorshipBordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043en_US
dc.description.sponsorshipDissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.en_US
dc.language.isoENen_US
dc.title.enPregnenolone blocks cannabinoid-induced acute psychotic-like states in mice
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/mp.2017.4en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed28220044en_US
dc.description.sponsorshipEuropeThe NGF system and its interplay with endocannabinoid signalling, from peripheral sensory terminals to the brain: new targets for the development of next generation drugs for neuropathic painen_US
dc.description.sponsorshipEuropeCannabinoid receptors CB1 in schizophrenia: role of brain mitochondrial activity and astroglial signallingen_US
dc.description.sponsorshipEuropeNeurocircuitry of endocannabinoid regulation of food intakeen_US
dc.description.sponsorshipEuropeDevelopment of pregnenolone derivatives as allosteric inhibitors of CB1 cannabinoid receptors for thetreatment of schizophrenia and psychotic syndromesen_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.page1594-1603en_US
bordeaux.volume22en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamNutrition, mémoire et glucocorticoïdesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDAgence Nationale de la Rechercheen_US
bordeaux.identifier.funderIDLabEx BRAINen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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