THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model

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• dc.contributor.author Cajiao-Manrique, María Del Mar
• dc.contributor.author Casadó-Anguera, Verònica
• dc.contributor.author García Blanco, Alejandra
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Martín García, Elena, 1975-
• dc.date.accessioned 2023-07-12T07:18:26Z
• dc.date.available 2023-07-12T07:18:26Z
• dc.date.issued 2023
• dc.description.abstract Background: Cannabis addiction is a chronically relapsing disorder lacking effective treatment. Regular cannabis consumption typically begins during adolescence, and this early cannabinoid exposure may increase the risk for drug addiction in adulthood. Objective: This study investigates the development of cannabis addiction-like behavior in adult mice after adolescent exposure to the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC). Methods: Adolescent male mice were exposed to 5 mg/kg of THC from postnatal days 37 to 57. Operant self-administration sessions of WIN 55,212-2 (12.5 μg/kg/infusion) were conducted for 10 days. Mice were tested for three addiction-like criteria (persistence of response, motivation, and compulsivity), two parameters related to craving (resistance to extinction and drug-seeking behavior), and two phenotypic vulnerability traits related to substance use disorders (impulsivity and reward sensitivity). Additionally, qPCR assays were performed to detect differentially expressed genes in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HPC) of "addicted" and "non-addicted" mice. Results: Adolescent THC exposure did not modify WIN 55,212-2 reinforcement nor the development of cannabis addiction-like behavior. Inversely, THC pre-exposed mice displayed impulsive-like behavior in adulthood, which was more pronounced in mice that developed the addiction-like criteria. Moreover, downregulated drd2 and adora2a gene expression in NAc and HPC was revealed in THC pre-exposed mice, as well as a downregulation of drd2 expression in mPFC of vehicle pre-treated mice that developed addiction-like behaviors. Discussion: These findings suggest that adolescent THC exposure may promote impulsivity-like behavior in adulthood, associated with downregulated drd2 and adora2a expression in NAc and HPC.
• dc.description.sponsorship This work was supported by the Spanish “Ministerio de Ciencia e Innovación (MICIN), Agencia Estatal de Investigación (AEI)” (PID2020-120029GB-I00/MICIN/AEI/10.13039/501100011033, R D21/0009/0019) to RM, the “Generalitat de Catalunya, AGAUR” (2017 SGR-669) to RM, the “ICREA-Acadèmia” (2020) to RM, the “European Commission-DG Research” (PainFact, H2020-SC1-2019-2-RTD-848099 and QSPain Relief, H2020-SC1-2019-2-RTD-848068) to RM, the Spanish “La Caixa” Foundation under the project code LCF/PR/HR22/52420017 to RM, the Spanish “Instituto de Salud Carlos III, RETICS-RTA” (RD16/0017/0020) to RM, the Spanish “Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas” (PNSD-2021I076 to RM and PNSD-2019I006 to EM-G), and Ministerio de Ciencia e Innovación (ERA-NET NEURON) PCI2021-122073-2A to EM-G. MC-M acknowledged the Generalitat de Catalunya and the AGAUR for a “FI-SDUR” scholarship (EMC/3345/2020). AG-B acknowledged the Generalitat de Catalunya and the AGAUR for the “FI” scholarship (FI_B00337_2020). VC-A acknowledged the Spanish MCIN/AEI/10.13039/501100011033 for a “Juan de la Cierva” fellowship (FJC2019-041020-I).
• dc.format.mimetype application/pdf
• dc.identifier.citation Cajiao-Manrique MM, Casadó-Anguera V, García-Blanco A, Maldonado R, Martín-García E. THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model. Front Psychiatry. 2023;14:1148993. DOI: 10.3389/fpsyt.2023.1148993
• dc.identifier.doi http://dx.doi.org/10.3389/fpsyt.2023.1148993
• dc.identifier.issn 1664-0640
• dc.identifier.uri http://hdl.handle.net/10230/57544
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Psychiatry. 2023;14:1148993
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848099
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848068
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-120029GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PCI2021-122073-2A
• dc.rights © 2023 Cajiao-Manrique, Casadó-Anguera, García-Blanco, Maldonado and Martín-García. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword THC
• dc.subject.keyword WIN 55,212-2 self-administration mouse model
• dc.subject.keyword Adolescence
• dc.subject.keyword Adora2a
• dc.subject.keyword Cannabis addiction
• dc.subject.keyword drd2
• dc.subject.keyword Impulsivity
• dc.title THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion