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A standardized protocol for repeated social defeat stress in mice

Nature Protocols volume 6, pages 11831191 (2011) | Download Citation

  • A Corrigendum to this article was published on 26 March 2015

This article has been updated


A major impediment to novel drug development has been the paucity of animal models that accurately reflect symptoms of affective disorders. In animal models, prolonged social stress has proven to be useful in understanding the molecular mechanisms underlying affective-like disorders. When considering experimental approaches for studying depression, social defeat stress, in particular, has been shown to have excellent etiological, predictive, discriminative and face validity. Described here is a protocol whereby C57BL/6J mice that are repeatedly subjected to bouts of social defeat by a larger and aggressive CD-1 mouse results in the development of a clear depressive-like syndrome, characterized by enduring deficits in social interactions. Specifically, the protocol consists of three important stages, beginning with the selection of aggressive CD-1 mice, followed by agonistic social confrontations between the CD-1 and C57BL/6J mice, and concluding with the confirmation of social avoidance in subordinate C57BL/6J mice. The automated detection of social avoidance allows a marked increase in throughput, reproducibility and quantitative analysis. This protocol is highly adaptable, but in its most common form it requires 3–4 weeks for completion.

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Change history

  • 17 December 2014

     In the version of this article initially published, there was some confusion over the interpretation of the sentence "Further, defeats should be run under constant veterinary evaluation and with full approval of all necessary institutional review boards and standards." For added clarity, the sentence was changed to read "Further, defeats should be run with full approval of all necessary institutional review boards and standards." The error has been corrected in the HTML and PDF versions of the article.


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We thank D. Christoffel for his helpful review of this manuscript. We also acknowledge the intrepid efforts of the Mount Sinai School of Medicine animal facility personnel. This research was supported by US National Institute of Mental Health grant 1R01MH090264-01A1.

Author information


  1. Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.

    • Sam A Golden
    •  & Scott J Russo
  2. Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York, USA.

    • Sam A Golden
    •  & Scott J Russo
  3. Department of Psychology, Duke University, Durham, North Carolina, USA.

    • Herbert E Covington III
  4. The Duke Institute for Brain Sciences, Duke University, Durham, North Carolina, USA.

    • Herbert E Covington III
  5. Department of Psychiatry, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, USA.

    • Olivier Berton


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S.A.G., H.E.C., O.B. and S.J.R. contributed to study design, data collection, analysis and writing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Scott J Russo.

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