Endocannabinoid-Mediated Plasticity in Nucleus Accumbens Controls Vulnerability to Anxiety after Social Defeat Stress
Cell Reports. 2016-08-01; 16(5): 1237-1242
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Bosch-Bouju C(1), Larrieu T(1), Linders L(1), Manzoni OJ(2), Layé S(3).
(1)Nutrition et Neurobiologie Intégrée, UMR 1286, INRA, 33000 Bordeaux, France; Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux University, 33000 Bordeaux, France.
(2)Aix-Marseille Université, 13009 Marseille, France; INSERM, 13009 Marseille, France; INMED UMR S 901, 13009 Marseille, France. Electronic address:
(3)Nutrition et Neurobiologie Intégrée, UMR 1286, INRA, 33000 Bordeaux, France; Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux University, 33000 Bordeaux, France. Electronic address: .
Chronic social defeat stress (CSDS) is a clinically relevant model of mood disorders. The relationship between the CSDS model and a physiologically pertinent paradigm of synaptic plasticity is not known. Here, we found that cluster analysis of the emotional behavior states of mice exposed to CSDS allowed their segregation into anxious and non-anxious groups. Endocannabinoid-mediated spike-timing dependent plasticity (STDP) in the nucleus accumbens was attenuated in non-anxious mice and abolished in anxious mice. Anxiety-like behavior in
stressed animals was specifically correlated with their ability to produce STDP. Pharmacological enhancement of 2-arachidonoyl glycerol (2-AG) signaling in the nucleus accumbens normalized the anxious phenotype and STDP in anxious mice. These data reveal that endocannabinoid modulation of synaptic efficacy in response to a naturalistic activity pattern is both a molecular correlate of behavioral adaptability and a crucial factor in the adaptive response to chronic stress.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.