Neurobiological sequelae of witnessing stressful events in adult mice

Brandon L. Warren, Vincent F. Vialou, Sergio D. Iñiguez, Lyonna F. Alcantara, Katherine N. Wright, Jiang Feng, Pamela J. Kennedy, Quincey Laplant, Li Shen, Eric J. Nestler, Carlos A. Bolaños-Guzmán

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


Background: It is well known that exposure to severe stress increases the risk for developing mood disorders. However, most chronic stress models in rodents involve at least some form of physically experiencing traumatic events. Methods: This study assessed the effects of a novel social stress paradigm that is insulated from the effects of physical stress. Specifically, adult male C57BL/6J mice were exposed to either emotional (ES) or physical stress (PS) for 10 minutes per day for 10 days. The ES mice were exposed to the social defeat of a PS mouse by a larger, more aggressive CD-1 mouse from the safety of an adjacent compartment. Results: Like PS mice, ES mice exhibited a range of depression- and anxiety-like behaviors both 24 hours and 1 month after the stress. Increased levels of serum corticosterone, part of the stress response, accompanied these behavioral deficits. Based on previous work that implicated gene expression changes in the ventral tegmental area (a key brain reward region) in the PS phenotype, we compared genome-wide mRNA expression patterns in this brain region of ES and PS mice using RNA-seq. We found significant overlap between these conditions, which suggests several potential gene targets for mediating the behavioral abnormalities observed. Conclusions: These findings demonstrate that witnessing traumatic events is a potent stress in adult male mice capable of inducing long-lasting neurobiological perturbations.

Original languageEnglish
Pages (from-to)7-14
Number of pages8
JournalBiological Psychiatry
Issue number1
StatePublished - 1 Jan 2013


  • Depression
  • RNA-seq
  • emotional stress
  • posttraumatic stress disorder
  • social defeat
  • ventral tegmental area


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