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Science 10 February 2006:
Vol. 311. no. 5762, pp. 864 - 868
DOI: 10.1126/science.1120972
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Reports

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}

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}utsouthwestern.edu

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