Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences
Commonly-used rodent tests of anxiety-like behavior lack predictive validity for human sex differences
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DOI：
10.1016/j.psyneuen.2022.105733
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发表时间：
2022-03-31
影响因子：
3.7
通讯作者：
Skibicka, Karolina P.
中科院分区：
文献类型：
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作者：
Borchers, Stina;Krieger, Jean-Philippe;Skibicka, Karolina P.
女性比男性更容易患上焦虑症。然而，焦虑的临床前模型主要是在雄性啮齿动物中开发的，对性别差异的预测有效性知之甚少。在这里，我们调查是否常用的焦虑样行为测试，高架十字迷宫（ESTA）和开放领域（OF），在成年Sprague-Dawley大鼠代表人类性别差异。当被解释为侧臂或OF时，与雄性相比，雌性大鼠表现出较少的焦虑样行为，因为与雄性相比，雌性大鼠在侧臂或OF中心的开放臂中花费的时间是雄性大鼠的两倍。然而，它们也表现出截然不同的运动活动水平，可能混淆了这些运动依赖性测试的解释。为了从评估中排除运动，使用了声惊吓反应（ASR）测试。当解释的ASR测试，女性表现出更多的焦虑样的行为相比，男性，由近两倍的惊吓幅度。观察到的性别差异不是由性腺类固醇驱动的。总的来说，除了一项测试外，所有测试都未能反映出人类焦虑的性别差异。我们的研究结果表明，ASR可能更适合模拟女性焦虑样行为。
Women are more likely to develop an anxiety disorder than men. Yet, preclinical models of anxiety were largely developed in male rodents, with poorly understood predictive validity for sex differences. Here, we investigate whether commonly-used anxiety-like behavior tests, elevated plus maze (EPM) and open field (OF), represent the human sex difference in adult Sprague-Dawley rats. When interpreted by EPM or OF, female rats displayed less anxiety-like behavior compared to males, as they spent twice as much time in the open arms of the EPM or the center of the OF compared to males. However, they also displayed vastly different levels of locomotor activity, possibly confounding interpretation of these locomotion-dependent tests. To exclude locomotion from the assessment, the acoustic startle response (ASR) test was used. When interpreted by the ASR test, females displayed more anxiety-like behavior compared to males, as indicated by a nearly two-fold higher startle amplitude. The observed sex differences were not driven by gonadal steroids. Overall, all but one of the tests fail to mirror the sex difference in anxiety reported in humans. Our findings suggest that the ASR might be a better fit in modelling female anxiety-like behavior.