ΔfosB in brain reward circuits mediates resilience to stress and antidepressant responses

Vincent Vialou, Alfred J. Robison, Quincey C. Laplant, Herbert E. Covington, David M. Dietz, Yoshinori N. Ohnishi, Ezekiell Mouzon, Augustus J. Rush, Emily L. Watts, Deanna L. Wallace, Sergio D. Ĩiguez, Yoko H. Ohnishi, Michel A. Steiner, Brandon L. Warren, Vaishnav Krishnan, Carlos A. Bolãos, Rachael L. Neve, Subroto Ghose, Olivier Berton, Carol A. TammingaEric J. Nestler

Research output: Contribution to journalArticle

291 Scopus citations

Abstract

In contrast with the many studies of stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. We found that the transcription factor ΔFosB mediates an essential mechanism of resilience in mice. Induction of ΔFosB in the nucleus accumbens, an important brain reward-associated region, in response to chronic social defeat stress was both necessary and sufficient for resilience. ΔFosB induction was also required for the standard antidepressant fluoxetine to reverse behavioral pathology induced by social defeat. ΔFosB produced these effects through induction of the GluR2 AMPA glutamate receptor subunit, which decreased the responsiveness of nucleus accumbens neurons to glutamate, and through other synaptic proteins. Together, these findings establish a previously unknown molecular pathway underlying both resilience and antidepressant action.

Original languageEnglish (US)
Pages (from-to)745-752
Number of pages8
JournalNature neuroscience
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Vialou, V., Robison, A. J., Laplant, Q. C., Covington, H. E., Dietz, D. M., Ohnishi, Y. N., Mouzon, E., Rush, A. J., Watts, E. L., Wallace, D. L., Ĩiguez, S. D., Ohnishi, Y. H., Steiner, M. A., Warren, B. L., Krishnan, V., Bolãos, C. A., Neve, R. L., Ghose, S., Berton, O., ... Nestler, E. J. (2010). ΔfosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nature neuroscience, 13(6), 745-752. https://doi.org/10.1038/nn.2551