Serum Response Factor Promotes Resilience to Chronic Social Stress through the Induction of ΔFosB

• DOI: 10.1523/jneurosci.2496-10.2010
• Publication Date: 2010-10-27T18:05:06Z
• Authors: Vincent Vialou; Ian Maze; William Renthal; Quincey C. LaPlant; Emily L. Watts; Ezekiell Mouzon; Subroto Ghose; Carol A. Tamminga; Eric J. Nestler
• Keywords: FOSB; Chronic Stress; Social defeat; JUNB

The molecular mechanisms underlying stress- and drug-induced neuronal adaptations are incompletely understood. One molecule implicated in such is ΔFosB, a transcription factor that accumulates the rodent nucleus accumbens (NAc), key brain reward region, response to either chronic stress or repeated exposure drugs of abuse. upstream transcriptional controlling ΔFosB induction by these environmental stimuli remain elusive. Here, we identify activity-dependent factor, serum (SRF), as novel mediator stress-, but not cocaine-, induced ΔFosB. SRF downregulated NAc both depressed human patients mice chronically exposed social defeat stress. This downregulation absent resilient animals. Through use inducible mutagenesis, show stress-mediated which occurs predominantly mice, dependent on expression this region. Furthermore, NAc-specific genetic deletion promotes variety prodepressant- proanxiety-like phenotypes renders animals more sensitive deleterious effects In contrast, demonstrate does play role accumulation cocaine exposure. knock-out has no effect cocaine-induced behaviors, indicating regulate behavioral sensitivity through independent mechanisms.