[从表现出行为无助的育种者中挑选出一种“抑郁”小鼠]。

J M Vaugeois, J Costentin
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引用次数: 0

摘要

抗抑郁药已经使用了40年。目前使用的所有抗抑郁药起效缓慢,并不能改善所有患者;因此,绝对需要新的抗抑郁药。各种各样的动物模型,通常基于抑郁症的单胺能理论,已被用于筛选当前的抗抑郁药。事实上,这些动物模型的主要重点是预测抗抑郁药物的潜力,即建立预测效度。然而,对这类动物模型的评估还应考虑面部有效性,即模型与人类状况的接近程度,这应有助于识别创新药物。当一个健康的人服用抗抑郁药时,只会产生与情绪无关的副作用,而它们会减轻抑郁症患者的抑郁症状。我们推测,基因选择的动物模型将比基于标准实验室菌株的模型更接近人类临床情况。我们在这里描述了小鼠品系之间在不动的数量上存在显著差异,即。“自发性无助”在悬尾试验中观察到,这是一种用于筛选潜在抗抑郁药物的方法。我们研究了在悬尾试验中选择性饲养的高或低不动分数小鼠的行为特征。有希望的是,这些选择性培育的品系将为研究抗抑郁作用的行为、神经化学和神经内分泌相关提供一种新的方法。
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[Creation of a line of "depressed" mice from a selection of breeders exhibiting a behavioral helplessness].

Antidepressants are used since 40 years. All presently used antidepressants have a slow onset of action and do not improve all patients; thus, there is an absolute need for new antidepressants. A variety of animal models, often based upon the monoaminergic theory of depressive disorders, has been used to screen the current antidepressants. In fact, the main focus of most of these animal models has been to predict the antidepressant potential i.e. to establish predictive validity. However, the evaluation of such animal models should also consider face validity, i.e. how closely the model resembles the human condition, and this should help to identify innovating medicines. Antidepressants, when taken by a healthy person, induce nothing more than side effects, unrelated to an action on mood, whereas they alleviate depressive symptomatology in depressed patients. We have speculated that genetically selected animal models would be closer to the human clinical situation than models based on standard laboratory strains. We have depicted here that marked differences exist between strains of mice in the amount of immobility i.e. "spontaneous helplessness" observed in the tail suspension test, a method used to screen potential antidepressants. We have studied the behavioural characteristics of mice selectively bred for spontaneous high or low immobility scores in the tail suspension test. Hopefully, these selectively bred lines will provide a novel approach to investigate behavioural, neurochemical and neuroendocrine correlates of antidepressant action.

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