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Science 311 (5762): 864-868

Copyright © 2006 by the American Association for the Advancement of Science

Essential Role of BDNF in the Mesolimbic Dopamine Pathway in Social Defeat Stress

Olivier Berton,1 Colleen A. McClung,1 Ralph J. DiLeone,* Vaishnav Krishnan,1 William Renthal,1 Scott J. Russo,1 Danielle Graham,1 Nadia M. Tsankova,1 Carlos A. Bolanos,{dagger} Maribel Rios,2 Lisa M. Monteggia,1 David W. Self,1 Eric J. Nestler{ddagger}

Abstract: Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway–specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.

1 Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390–9070, USA.
2 Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.

* Present address: Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.

{dagger} Present address: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, FL 32306–1270, USA.

{ddagger} To whom correspondence should be addressed. E-mail: eric.nestler{at}

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C. A. Winstanley, Q. LaPlant, D. E. H. Theobald, T. A. Green, R. K. Bachtell, L. I. Perrotti, R. J. DiLeone, S. J. Russo, W. J. Garth, D. W. Self, et al. (2007)
J. Neurosci. 27, 10497-10507
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Brain-Derived Neurotrophic Factor: Linking Fear Learning to Memory Consolidation.
M.-H. Monfils, K. K. Cowansage, and J. E. LeDoux (2007)
Mol. Pharmacol. 72, 235-237
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Environment and Schizophrenia: Environmental Factors in Schizophrenia: Childhood Trauma--A Critical Review.
C. Morgan and H. Fisher (2007)
Schizophr Bull 33, 3-10
   Abstract »    Full Text »    PDF »
Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli..
T. A. Green, I. N. Alibhai, J. D. Hommel, R. J. DiLeone, A. Kumar, D. E. Theobald, R. L. Neve, and E. J. Nestler (2006)
J. Neurosci. 26, 8235-8242
   Abstract »    Full Text »    PDF »
Applying Transdisciplinary Research Strategies to Understanding and Eliminating Health Disparities.
D. B. Abrams (2006)
Health Educ Behav 33, 515-531
   Abstract »    PDF »
Social Adversity and Neuronal Resiliency: Two Animal Studies.
Journal Watch Psychiatry 2006, 6
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