Departments of Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, AB Canada.
Neurosci Biobehav Rev. 2012 Oct;36(9):2085-117. doi: 10.1016/j.neubiorev.2012.07.001. Epub 2012 Jul 7.
The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression.
慢性轻度（或不可预测/多变）应激（CMS）模型是 20 多年前作为一种抑郁症动物模型开发的。该模型的基础是，长期暴露于一系列轻度但不可预测的应激源后，动物会出现奖赏效能降低的状态，类似于重性抑郁障碍中观察到的快感缺失。自成立以来，尽管该模型从未经过严格检查以验证 CMS 引起的神经生物学变化与抑郁障碍中记录的变化平行，但该模型也被用于各种研究，以检查与抑郁相关的神经生物学变量。目前综述的目的是总结慢性轻度应激对神经生物学变量的影响，如神经化学、神经化学受体表达和功能、神经营养因子表达和细胞可塑性。然后将这些发现与临床研究中检查抑郁障碍人群中的常见变量进行比较，以确定慢性轻度应激后观察到的变化是否与重性抑郁障碍中观察到的变化一致。我们得出结论，慢性轻度应激范式：（1）引起一系列与抑郁障碍中观察到的变化相似的神经生物学变化；（2）可能是一种合适的工具，可以研究在抑郁中可能受到干扰的新系统，从而有助于开发治疗抑郁的新靶点。
