Delta FosB in brain reward circuits mediates resilience to stress and antidepressant responses

作者：Vialou Vincent; Robison Alfred J; LaPlant Quincey C; Covington Herbert E III; Dietz David M; Ohnishi Yoshinori N; Mouzon Ezekiell; Rush Augustus J III; Watts Emily L; Wallace Deanna L; Iniguez Sergio D; Ohnishi Yoko H; Steiner Michel A; Warren Brandon L; Krishnan Vaishnav; Bolanos Carlos A; Neve Rachael L; Ghose Subroto; Berton Olivier; Tamminga Carol A; Nestler Eric J^*

来源：Nature Neuroscience, 2010, 13(6): 745-U126.

DOI：10.1038/nn.2551

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 Delta FosB mediates an essential mechanism of resilience in mice. Induction of Delta FosB in the nucleus accumbens, an important brain reward-associated region, in response to chronic social defeat stress was both necessary and sufficient for resilience. Delta FosB induction was also required for the standard antidepressant fluoxetine to reverse behavioral pathology induced by social defeat. Delta FosB 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.

• 出版日期2010-6