Cryan J F, Mombereau C
Neuroscience Research, The Novartis Institutes for BioMedical Research, Basel, Switzerland.
Mol Psychiatry. 2004 Apr;9(4):326-57. doi: 10.1038/sj.mp.4001457.
The ability to modify mice genetically has been one of the major breakthroughs in modern medical science affecting every discipline including psychiatry. It is hoped that the application of such technologies will result in the identification of novel targets for the treatment of diseases such as depression and to gain a better understanding of the molecular pathophysiological mechanisms that are regulated by current clinically effective antidepressant medications. The advent of these tools has resulted in the need to adopt, refine and develop mouse-specific models for analyses of depression-like behavior or behavioral patterns modulated by antidepressants. In this review, we will focus on the utility of current models (eg forced swim test, tail suspension test, olfactory bulbectomy, learned helplessness, chronic mild stress, drug-withdrawal-induced anhedonia) and research strategies aimed at investigating novel targets relevant to depression in the mouse. We will focus on key questions that are considered relevant for examining the utility of such models. Further, we describe other avenues of research that may give clues as to whether indeed a genetically modified animal has alterations relevant to clinical depression. We suggest that it is prudent and most appropriate to use convergent tests that draw on different antidepressant-related endophenotypes, and complimentary physiological analyses in order to provide a program of information concerning whether a given phenotype is functionally relevant to depression-related pathology.
对小鼠进行基因改造的能力一直是现代医学科学的重大突破之一，影响着包括精神病学在内的各个学科。人们希望应用此类技术能够确定治疗抑郁症等疾病的新靶点，并更好地理解当前临床有效抗抑郁药物所调控的分子病理生理机制。这些工具的出现导致需要采用、完善和开发针对小鼠的模型，用于分析类似抑郁的行为或抗抑郁药调节的行为模式。在本综述中，我们将重点关注当前模型（如强迫游泳试验、悬尾试验、嗅球切除、习得性无助、慢性轻度应激、药物戒断诱导的快感缺失）的效用以及旨在研究与小鼠抑郁症相关新靶点的研究策略。我们将聚焦于与评估此类模型效用相关的关键问题。此外，我们还描述了其他研究途径，这些途径可能为判断转基因动物是否确实存在与临床抑郁症相关的改变提供线索。我们建议，谨慎且最合适的做法是采用基于不同抗抑郁相关内表型的聚合试验以及补充性生理分析，以便提供有关给定表型是否与抑郁症相关病理在功能上相关的信息方案。
