Early 5-HT6 receptor blockade prevents symptom onset in a model of adolescent cannabis abuse

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• dc.contributor.author Berthoux, Coralie
• dc.contributor.author Hamieh, Al Mahdy
• dc.contributor.author Rogliardo, Angelina
• dc.contributor.author Doucet, Emilie L.
• dc.contributor.author Coudert, Camille
• dc.contributor.author Ango, Fabrice
• dc.contributor.author Grychowska, Katarzyna
• dc.contributor.author Chaumont-Dubel, Séverine
• dc.contributor.author Zajdel, Pawel
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Bockaert, Joël
• dc.contributor.author Marin, Philippe
• dc.contributor.author Bécamel, Carine
• dc.date.accessioned 2020-05-07T07:05:01Z
• dc.date.available 2020-05-07T07:05:01Z
• dc.date.issued 2020
• dc.description.abstract Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR activation in cognitive deficits of rodent developmental models of schizophrenia, we show that chronic administration of ∆9-tetrahydrocannabinol (THC) to mice during adolescence induces a long-lasting activation of mTOR in prefrontal cortex (PFC), alterations of excitatory/inhibitory balance, intrinsic properties of layer V pyramidal neurons, and long-term depression, as well as cognitive deficits in adulthood. All are prevented by administrating a 5-HT6 receptor antagonist or rapamycin, during adolescence. In contrast, they are still present 2 weeks after the same treatments delivered at the adult stage. Collectively, these findings suggest a role of 5-HT6 receptor-operated mTOR signaling in abnormalities of cortical network wiring elicited by THC at a critical period of PFC maturation and highlight the potential of 5-HT6 receptor antagonists as early therapy to prevent cognitive symptom onset in adolescent cannabis abusers.
• dc.format.mimetype application/pdf
• dc.identifier.citation Berthoux C, Hamieh AM, Rogliardo A, Doucet EL, Coudert C, Ango F, Grychowska K, Chaumont-Dubel S, Zajdel P, Maldonado R, Bockaert J, Marin P, Bécamel C. Early 5-HT6 receptor blockade prevents symptom onset in a model of adolescent cannabis abuse. EMBO Mol Med. 2020; 12(5):e10605. DOI: 10.15252/emmm.201910605
• dc.identifier.doi http://dx.doi.org/10.15252/emmm.201910605
• dc.identifier.issn 1757-4676
• dc.identifier.uri http://hdl.handle.net/10230/44440
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof EMBO Mol Med. 2020; 12(5):e10605
• dc.rights © 2020 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword mTOR
• dc.subject.keyword 5HT6 receptor
• dc.subject.keyword Adolescent cannabis abusers
• dc.subject.keyword Cognitive deficits
• dc.subject.keyword Synaptic transmission
• dc.title Early 5-HT6 receptor blockade prevents symptom onset in a model of adolescent cannabis abuse
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion