Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States.
Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan.
Sci Rep. 2017 Oct 9;7(1):12838. doi: 10.1038/s41598-017-12811-8.
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.
许多研究采用重复社交挫败应激（RSDS）来研究啮齿动物抑郁的神经生物学机制。迄今为止，RSDS 研究的一个重要局限性是，由于难以发起针对雌性小鼠的攻击行为，这些研究仅在雄性小鼠中进行。在这里，我们通过化学遗传激活腹内侧下丘脑的腹外侧亚区（VMHvl）来诱导雄性对雌性的攻击，从而建立了雌性小鼠 RSDS 模型。我们证明，易受 RSDS 影响的雌性表现出社交回避、类似焦虑的行为、体重减轻和循环白细胞介素 6 水平升高。相比之下，我们称之为具有弹性的一小部分小鼠在 RSDS 后仅表现出类似焦虑的行为。该模型允许研究性别差异在挫败诱导的抑郁样行为的神经生物学机制中的作用。一个强大的雌性社交挫败模型是鉴定和开发新型治疗化合物以治疗女性抑郁和焦虑障碍的关键第一步。
