Cryan John F, Markou Athina, Lucki Irwin
Neuromodulation Unit, Nervous System Research, Novartis Pharma AG, WSJ 386.344, CH-4002 Basel, Switzerland.
Trends Pharmacol Sci. 2002 May;23(5):238-45. doi: 10.1016/s0165-6147(02)02017-5.
Animal models are indispensable tools in the search to identify new antidepressant drugs and to provide insights into the neuropathology that underlies the idiopathic disease state of depression. As new targets are developed, both serendipitously and through hypothesis-driven research, existing animal paradigms are being modified and new tests are being developed to detect antidepressant actions of compounds acting on a broad range of neural and genetic targets. This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential. Emphasis is placed on recent modifications to such paradigms that have increased their utility and reliability. Furthermore, some key issues that need to be addressed for future discovery of novel antidepressant agents are examined, and the available data on genetically altered mice that might lead to the discovery of novel targets for antidepressant action are collated.
动物模型是寻找新型抗抑郁药物以及深入了解抑郁症特发性疾病状态背后神经病理学的不可或缺的工具。随着新靶点通过偶然发现和基于假设的研究得以开发,现有的动物模型正在被修改,同时也在开发新的测试方法,以检测作用于广泛神经和遗传靶点的化合物的抗抑郁作用。本综述聚焦于目前用于预测抗抑郁潜力的一些最广泛使用的动物模型的最新研究结果。重点在于近期对这些模型的改进,这些改进提高了它们的实用性和可靠性。此外,还探讨了未来发现新型抗抑郁药物需要解决的一些关键问题,并整理了有关基因改造小鼠的现有数据,这些数据可能会促成抗抑郁作用新靶点的发现。