A male mouse model of WIN 55,212-2 self-administration to study cannabinoid addiction

A male mouse model of WIN 55,212-2 self-administration to study cannabinoid addiction

Cajiao-Manrique, María del Mar (Universitat Pompeu Fabra. Laboratory of Neuropharmacology-Neurophar)
Maldonado, Rafael (Institut Hospital del Mar d’Investigacions Mèdiques)
Martín García, Elena (Universitat Autònoma de Barcelona. Departament de Psicobiologia i Metodologia de les Ciències de la Salut)

Data: 2023
Resum: We have established for the first time a mouse model of cannabinoid addiction using WIN 55,212-2 intravenous self-administration (0. 0125 mg/kg/infusion) in C57Bl/6J mice. This model allows to evaluate the addiction criteria by grouping them into 1) persistence of response during a period of non-availability of the drug, 2) motivation for WIN 55,212-2 with a progressive ratio, and 3) compulsivity when the reward is associated with a punishment such as an electric foot-shock, in agreement with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). This model also allows to measure two parameters that have been related with the DSM-5 diagnostic criteria of craving, resistance to extinction and reinstatement, and two phenotypic traits suggested as predisposing factors, impulsivity and sensitivity to reward. We found that 35. 6% of mice developed the criteria of cannabinoid addiction, allowing to differentiate between resilient and vulnerable mice. Therefore, we have established a novel and reliable model to study the neurobiological correlates underlying the resilience or vulnerability to develop cannabinoid addiction. This model included the chemogenetic inhibition of neuronal activity in the medial prefrontal cortex to the nucleus accumbens pathway to assess the neurobiological substrate of cannabinoid addiction. This model will shed light on the neurobiological substrate underlying cannabinoid addiction.
Ajuts: Agencia Estatal de Investigación PID 2020- 120029GB-I00/MICIN/AEI/10.13039/501100011033, RD21/0009/0019
Agència de Gestió d’Ajuts Universitaris i de Recerca 2017-SGR-669
European Commission. Horizon 2020 H2020-SC1-2019-2-RTD-848099
European Commission. Horizon 2020 H2020-SC1-2019-2-RTD-848068
“la Caixa” Foundation LCF/PR/HR22/52420017
Instituto de Salud Carlos III RD16/0017/0020
Ministerio de Sanidad, Servicios Sociales e Igualdad PNSD- 2021I076 PNSD- 2019I006
Ministerio de Ciencia e Innovación PCI 2021-122073-2A

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. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Cannabinoid addiction ;
Mouse model ;
WIN 55,212-2 self-administration ;
Persistence of response ;
Motivation ;
Compulsive-like behavior
Publicat a: Frontiers in Pharmacology, Vol. 14 (march 2023) , ISSN 1663-9812

DOI: 10.3389/fphar.2023.1143365

PMID: 37050910


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