The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake

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• dc.contributor.author Luján Pérez, Miguel Ángel, 1991-
• dc.contributor.author Cantacorps Centellas, Lídia, 1991-
• dc.contributor.author Valverde Granados, Olga
• dc.date.accessioned 2020-05-08T08:20:32Z
• dc.date.issued 2020
• dc.description.abstract The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self-administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6-day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol-induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol-induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.
• dc.description.sponsorship This work was supported by Ministerio de Economía y Competitividad (grant number SAF2016-75966-R-FEDER), by the European Union's Horizon 2020 research andinnovation programme 2014–2020 under grant agreement no 634143. M.A.L. received FPU grant (15/02492) from the Ministeriode Educacion, Cultura y Deporte. L.C.received FPI grant(BES-2014-070657) from the Ministerio de Economía y Competitividad.The Department of Experimental and Health Sciences (UPF) is an“Unidad de Excelencia María de Maeztu” funded by the MINECO (Ref. MDM-2014-0370).The authors thank Gerald-Patrick Fannon for his English proofreading and editing of the manuscript, and Phytoplant Research S.L. for providing CBD compound.The authors declare no conflicts of interest. AUTHORS CONTRIBUTION M.A.L. and O.V. were responsible for the study concept and design.M.A.L .and L.C carried out the experimental studies. M.A.L. and O.V.drafted the manuscript and editing of the manuscript, and Phytoplant Research S.L. for providing CBD compound.The authors declare no conflicts of interest.
• dc.format.mimetype application/pdf
• dc.identifier.citation Luján MÁ, Cantacorps L, Valverde O. The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake. Addict Biol. 2020 Jul; 25(4):e12778. DOI: 10.1111/adb.12778
• dc.identifier.doi http://dx.doi.org/10.1111/adb.12778
• dc.identifier.issn 1355-6215
• dc.identifier.uri http://hdl.handle.net/10230/44465
• dc.language.iso eng
• dc.publisher Wiley-Blackwell
• dc.relation.ispartof Addiction Biology. 2020 Jul; 25(4):e12778
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634143
• dc.rights This is the pre-peer reviewed version of the following article: Luján MÁ, Cantacorps L, Valverde O. The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake. Addict Biol. 2019 Jun 4:e12778, which has been published in final form at http://dx.doi.org/10.1111/adb.12778. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Cannabidiol
• dc.subject.keyword Cocaine
• dc.subject.keyword Neurogenesis
• dc.subject.keyword Reinforcement
• dc.subject.keyword Self-administration
• dc.subject.keyword Temozolomide
• dc.title The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion