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作为评估抗抑郁活性模型的悬尾试验:小鼠药理学和遗传学研究综述

The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.

作者信息

Cryan John F, Mombereau Cedric, Vassout Annick

机构信息

Psychiatry Program, Neuroscience Research, The Novartis Institutes for BioMedical Research WSJ 386.344, Novartis Pharma AG., CH-4002 Basel, Switzerland.

出版信息

Neurosci Biobehav Rev. 2005;29(4-5):571-625. doi: 10.1016/j.neubiorev.2005.03.009.

DOI:10.1016/j.neubiorev.2005.03.009
PMID:15890404
Abstract

Since its introduction almost 20 years ago, the tail suspension test has become one of the most widely used models for assessing antidepressant-like activity in mice. The test is based on the fact that animals subjected to the short-term, inescapable stress of being suspended by their tail, will develop an immobile posture. Various antidepressant medications reverse the immobility and promote the occurrence of escape-related behaviour. This review focuses on the utility this test as part of a research program aimed at understanding the mechanism of action of antidepressants. We discuss the inherent difficulties in modeling depression in rodents. We describe how the tail suspension differs from the closely related forced swim test. Further, we address some key issues associated with using the TST as a model of antidepressant action. We discuss issues regarding whether it satisfies criteria to be a valid model for assessing depression-related behavioural traits. We elaborate on the tests' ease of use, strain differences observed in the test and gender effects in the test. We focus on the utility of the test for genetic analysis. Furthermore, we discuss the concept of whether immobility maybe a behavioural trait relevant to depression. All of the available pharmacological data using the test in genetically modified mice is collated. Special attention is given to selective breeding programs such as the Rouen 'depressed' mice which have been bred for high and low immobility in the tail suspension test. We provide an extensive pooling of the pharmacological studies published to date using the test. Finally, we provide novel pharmacological validation of an automated system (Bioseb) for assessing immobility. Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.

摘要

自近20年前引入以来,悬尾试验已成为评估小鼠抗抑郁样活性最广泛使用的模型之一。该试验基于这样一个事实,即遭受短期、无法逃避的尾巴悬吊应激的动物会出现静止不动的姿势。各种抗抑郁药物可逆转这种静止不动状态并促进与逃避相关行为的发生。本综述重点关注该试验作为旨在了解抗抑郁药作用机制的研究计划一部分的效用。我们讨论了在啮齿动物中模拟抑郁症的内在困难。我们描述了悬尾试验与密切相关的强迫游泳试验有何不同。此外,我们讨论了与将悬尾试验用作抗抑郁作用模型相关的一些关键问题。我们讨论了它是否符合作为评估与抑郁症相关行为特征的有效模型的标准的问题。我们详细阐述了该试验的易用性、试验中观察到的品系差异以及试验中的性别效应。我们重点关注该试验在遗传分析中的效用。此外,我们讨论了静止不动是否可能是与抑郁症相关的行为特征的概念。整理了在转基因小鼠中使用该试验获得的所有可用药理学数据。特别关注了选择性育种计划,例如在悬尾试验中为高静止不动和低静止不动而培育的鲁昂“抑郁”小鼠。我们广泛汇总了迄今为止使用该试验发表的药理学研究。最后,我们为评估静止不动的自动化系统(Bioseb)提供了新的药理学验证。综上所述,我们得出结论,悬尾试验是评估抗抑郁化合物以及与抑郁症相关的其他药理学和基因操作的行为效应的有用试验。

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