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Science 339 (6117): 332-335

Copyright © 2013 by the American Association for the Advancement of Science

Chronic Stress Triggers Social Aversion via Glucocorticoid Receptor in Dopaminoceptive Neurons

Jacques Barik,1,2,3,4,* Fabio Marti,3,4,5 Carole Morel,3,4,5 Sebastian P. Fernandez,3,4,6 Christophe Lanteri,2,3,7 Gérard Godeheu,2,3,7 Jean-Pol Tassin,2,3,7 Cédric Mombereau,3,4,8 Philippe Faure,3,4,5 François Tronche1,2,3,4,*

Abstract: Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

1 Molecular Genetics, Neurophysiology and Behavior Group, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7224, 75005 Paris, France.
2 Institut National de la Santé et de la Recherche Médicale (INSERM) U952S, 75005 Paris, France.
3 Université Pierre et Marie Curie, 75005 Paris, France.
4 Laboratory of Excellence (Labex) Biological Psychiatry Laboratory, 75005 Paris, France.
5 Neurophysiology and Behavior Group, CNRS UMR7102, 75005 Paris, France.
6 Neurotransmission and Development Group, INSERM U839, 75005 Paris, France.
7 Physiopathology of Addiction and Relapse Group, CNRS UMR7224, 75005 Paris, France.
8 Molecular and Cellular Mechanisms of Cortical Development Group, INSERM U839, 75005 Paris, France.

* To whom correspondence should be addressed. E-mail: francois.tronche{at}upmc.fr (F.T.); jacques.barik{at}snv.jussieu.fr (J.B.)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hormones and the Social Brain.
B. S. McEwen (2013)
Science 339, 279-280
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