Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine |
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| Authors: | Jean‐François De Backer Stéphanie Monlezun Bérangère Detraux Adeline Gazan Laura Vanopdenbosch Julian Cheron Giuseppe Cannazza Sébastien Valverde Lídia Cantacorps Mérie Nassar Alban de Kerchove d'Exaerde |
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| Affiliation: | 1. Laboratoire de Neurophysiologie, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium;2. Dipartimento di Scienze della Vita, Centro di Neuroscienze e Neurotecnologie, Università degli Studi di Modena e Reggio Emilia, Modena, Italy;3. INSERM, CNRS, Neuroscience Paris Seine ‐ Institut de Biologie Paris Seine (NPS ‐ IBPS), UPMC Univ Paris 06, Sorbonne Universités, Paris, France;4. Departament de Ciències Experimentals i de la Salut, Grup de Recerca en Neurobiologia del Comportament (GReNeC), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelone, Spain;5. Center for Interdisciplinary Research in Biology, Collège de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France;6. WELBIO, Brussels, Belgium |
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| Abstract: | 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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| Keywords: | amygdala dopamine drug sensitization nucleus accumbens prefrontal cortex |
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