THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model
Cajiao-Manrique, María del Mar (Universitat Pompeu Fabra)
Casadó-Anguera, Verònica (Universitat Pompeu Fabra)
García-Blanco, Alejandra (Universitat Pompeu Fabra)
Maldonado, Rafael 1961- (Institut Hospital del Mar d'Investigacions Mèdiques)
Martín-García, Elena, 1975- (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)

Data:	2023
Resum:	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. This study investigates the development of cannabis addiction-like behavior in adult mice after adolescent exposure to the main psychoactive component of cannabis, Δ 9 -tetrahydrocannabinol (THC). 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. 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. 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.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca EMC/3345/2020 Agència de Gestió d'Ajuts Universitaris i de Recerca FI_B00337_2020 Ministerio de Ciencia e Innovación FJC2019-041020-I Ministerio de Ciencia e Innovación PID2020-120029GB-I00 Ministerio de Ciencia e Innovación PCI2021-122073-2A Ministerio de Sanidad, Servicios Sociales e Igualdad PNSD-2021I076 Ministerio de Sanidad, Servicios Sociales e Igualdad PNSD-2019I006 Ministerio de Ciencia, Innovación y Universidades PCI2021-122073-2A Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-669 European Commission. Horizon 2020 848099 European Commission. Horizon 2020 848068 Instituto de Salud Carlos III RD16/0017/0020 "la Caixa" Foundation RD16/0017/0020
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cannabis addiction ; Adolescence ; WIN 55,212-2 self-administration mouse model ; THC ; Impulsivity ; Drd2 ; Adora2a
Publicat a:	Frontiers in psychiatry, Vol. 14 (may 2023) , ISSN 1664-0640

DOI: 10.3389/fpsyt.2023.1148993
PMID: 37304451

19 p, 5.8 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats