[Delta]FosB in brain reward circuits mediates resilience to stress and antidepressant responses : Nature Neuroscience : Nature Publishing Group

ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses
Vincent Vialou,Alfred J Robison,Quincey C LaPlant,Herbert E Covington III,David M Dietz,Yoshinori N Ohnishi,Ezekiell Mouzon,Augustus J Rush III,Emily L Watts,Deanna L Wallace,Sergio D Iñiguez,Yoko H Ohnishi,Michel A Steiner,Brandon L Warren,Vaishnav Krishnan,Carlos A Bolaños,Rachael L Neve,Subroto Ghose,Olivier Berton,Carol A Tamminga& Eric J Nestler

Corresponding author Journal name:
Nature Neuroscience

Year published:
(2010)

DOI:
doi:10.1038/nn.2551

Received 01 February 2010
Accepted 12 April 2010
Published online 16 May 2010

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.

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[Delta]FosB in brain reward circuits mediates resilience to stress and antidepressant responses : Nature Neuroscience : Nature Publishing Group