Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2012;7(10):e48414. doi: 10.1371/journal.pone.0048414. Epub 2012 Oct 31.
Animal models of human diseases of the central nervous system, generalized anxiety disorder included, are essential for the study of the brain-behavior interface and obligatory for drug development; yet, these models fail to yield new insights and efficacious drugs. By increasing testing duration hundredfold and arena size tenfold, and comparing the behavior of the common animal model to that of wild mice, we raise concerns that chronic anxiety might have been measured at the wrong time, for the wrong duration, and in the wrong animal. Furthermore, the mice start the experimental session with a short period of transient adaptation to the novel environment (habituation period) and a long period reflecting the respective trait of the mice. Using common measures of anxiety reveals that mice exhibit opposite results during these periods suggesting that chronic anxiety should be measured during the post-habituation period. We recommend tools for measuring the transient period, and provide suggestions for characterizing the post habituation period.
中枢神经系统人类疾病的动物模型,包括广泛性焦虑障碍,对于研究大脑-行为界面至关重要,也是药物开发所必需的;然而,这些模型未能提供新的见解和有效的药物。通过将测试持续时间增加一百倍,将竞技场大小增加十倍,并将常见动物模型的行为与野生老鼠的行为进行比较,我们担心慢性焦虑可能在错误的时间、错误的持续时间和错误的动物中进行了测量。此外,老鼠在实验开始时会经历一个短暂的适应新环境的阶段(习惯化阶段)和一个反映老鼠各自特征的阶段。使用常见的焦虑测量方法表明,老鼠在这些阶段表现出相反的结果,这表明慢性焦虑应该在习惯化后阶段进行测量。我们建议使用测量短暂阶段的工具,并提供了用于描述习惯化后阶段的建议。