Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine

Melanoma antigen genes (Mage) were first described as tumour markers. However, some of Mage are also expressed in healthy cells where their functions remain poorly understood. Here, we describe an unexpected role for one of these genes, Maged1, in the control of behaviours related to drug addiction....

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Detalles Bibliográficos
Autores: De Backer, Jean-François, Monlezun, Stéphanie, Detraux, Bérangère, Gazan, Adeline, Vanopdenbosch, Laura, Cheron, Julian, Cannazza, Giuseppe, Valverde, Sébastien, Cantacorps Centellas, Lídia, 1991-, Nassar, Mérie, Venance, Laurent, Valverde Granados, Olga, Faure, Philippe, Zoli, Michele, De Backer, Olivier, Gall, David, Schiffmann, Serge N., de Kerchove d'Exaerde, Alban
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/37044
Acceso en línea:http://hdl.handle.net/10230/37044
http://dx.doi.org/10.15252/embr.201745089
Access Level:acceso abierto
Palabra clave:Amygdala
Dopamine
Drug sensitization
Nucleus accumbens
Prefrontal cortex
Descripción
Sumario:Melanoma antigen genes (Mage) were first described as tumour markers. However, some of Mage are also expressed in healthy cells where their functions remain poorly understood. Here, we describe an unexpected role for one of these genes, Maged1, in the control of behaviours related to drug addiction. Mice lacking Maged1 are insensitive to the behavioural effects of cocaine as assessed by locomotor sensitization, conditioned place preference (CPP) and drug self-administration. Electrophysiological experiments in brain slices and conditional knockout mice demonstrate that Maged1 is critical for cortico-accumbal neurotransmission. Further, expression of Maged1 in the prefrontal cortex (PFC) and the amygdala, but not in dopaminergic or striatal and other GABAergic neurons, is necessary for cocaine-mediated behavioural sensitization, and its expression in the PFC is also required for cocaine-induced extracellular dopamine (DA) release in the nucleus accumbens (NAc). This work identifies Maged1 as a critical molecule involved in cellular processes and behaviours related to addiction.

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