Cocaine-seeking behaviour is differentially expressed in male and female mice exposed to maternal separation and is associated with alterations in AMPA receptors subunits in the medial prefrontal cortex

According with clinical data, women evolve differently from drug use to drug abuse. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that females show increased motivation to seek cocaine during the self-administration paradigm (SA) than males. Moreover...

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Detalhes bibliográficos
Autores: Castro Zavala, Adriana, 1988-, Martín Sánchez, Ana, Montalvo-Martínez, Larisa, Camacho-Morales, Alberto, Valverde Granados, Olga
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/48999
Acesso em linha:http://hdl.handle.net/10230/48999
http://dx.doi.org/10.1016/j.pnpbp.2021.110262
Access Level:acceso abierto
Palavra-chave:Cocaine self-administration
Despair-like behaviour
GluA1
GluA2
Gria1
Gria2
Descrição
Resumo:According with clinical data, women evolve differently from drug use to drug abuse. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that females show increased motivation to seek cocaine during the self-administration paradigm (SA) than males. Moreover, suffering childhood adversity or major depressive disorder are two factors that could increase the predisposition to suffer cocaine addiction. Maternal separation with early weaning (MSEW) is an animal model that allows examining the impact of early-life stress on cocaine abuse. In this study, we aimed to explore changes in MSEW-induced cocaine-seeking motivation to determine potential associations between despair-like behaviour and cocaine-seeking. We also evaluated possible alterations in the AMPA receptors (AMPArs) composition in the medial prefrontal cortex (mPFC) of these mice. We exposed mice to MSEW and the behavioural tests were performed during adulthood. Moreover, GluA1, GluA2 mRNA and protein expression were evaluated in the mPFC. Results show higher cocaine-seeking in standard nest females, as well as an increase in GluA1 and GluA2 protein expression. Moreover, MSEW induces downregulation of Gria2 and increases the Gria1/Gria2 ratio, only in male mice. In conclusion, female mice show different composition of the AMPA receptor in the mPFC and MSEW alters the glutamatergic system in the mPFC of male mice.