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Sci Rep. 2017 Oct 9;7(1):12838. doi: 10.1038/s41598-017-12811-8.

Establishment of a repeated social defeat stress model in female mice.

Author information

1
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States.
2
Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan.
3
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, 10065, United States.
4
Department of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States.
5
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States. scott.russo@mssm.edu.

Abstract

Numerous studies have employed repeated social defeat stress (RSDS) to study the neurobiological mechanisms of depression in rodents. An important limitation of RSDS studies to date is that they have been conducted exclusively in male mice due to the difficulty of initiating attack behavior directed toward female mice. Here, we establish a female mouse model of RSDS by inducing male aggression toward females through chemogenetic activation of the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate that females susceptible to RSDS display social avoidance, anxiety-like behavior, reduction of body weight, and elevated levels of circulating interleukin 6. In contrast, a subset of mice we term resilient only display anxiety-like behaviors after RSDS. This model allows for investigation of sex differences in the neurobiological mechanisms of defeat‒induced depression‒like behaviors. A robust female social defeat model is a critical first step in the identification and development of novel therapeutic compounds to treat depression and anxiety disorders in women.

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