Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Nat Protoc. 2011 Jul 21;6(8):1183-91. doi: 10.1038/nprot.2011.361.
A major impediment to novel drug development has been the paucity of animal models that accurately reflect symptoms of affective disorders. In animal models, prolonged social stress has proven to be useful in understanding the molecular mechanisms underlying affective-like disorders. When considering experimental approaches for studying depression, social defeat stress, in particular, has been shown to have excellent etiological, predictive, discriminative and face validity. Described here is a protocol whereby C57BL/6J mice that are repeatedly subjected to bouts of social defeat by a larger and aggressive CD-1 mouse results in the development of a clear depressive-like syndrome, characterized by enduring deficits in social interactions. Specifically, the protocol consists of three important stages, beginning with the selection of aggressive CD-1 mice, followed by agonistic social confrontations between the CD-1 and C57BL/6J mice, and concluding with the confirmation of social avoidance in subordinate C57BL/6J mice. The automated detection of social avoidance allows a marked increase in throughput, reproducibility and quantitative analysis. This protocol is highly adaptable, but in its most common form it requires 3-4 weeks for completion.
新型药物开发的主要障碍一直是缺乏能够准确反映情感障碍症状的动物模型。在动物模型中，长期的社会压力已被证明有助于理解情感障碍相关的分子机制。在考虑用于研究抑郁症的实验方法时，社会挫败应激，特别是，已被证明具有极好的病因学、预测性、鉴别性和相似性。本文描述了一种方案，通过该方案，反复受到更大、更具攻击性的 CD-1 小鼠社会挫败的 C57BL/6J 小鼠会发展出明显的抑郁样综合征，其特征是社会互动持久缺陷。具体来说，该方案由三个重要阶段组成，首先是选择具有攻击性的 CD-1 小鼠，然后是 CD-1 和 C57BL/6J 小鼠之间的对抗性社会对抗，最后是确认从属的 C57BL/6J 小鼠的社会回避。社会回避的自动检测允许显著提高吞吐量、重现性和定量分析。该方案具有高度适应性，但在最常见的形式下，它需要 3-4 周才能完成。
