New behavioral animal model to study vulnerability factors for depression

我们通过修改小鼠的水迷宫学习任务，开发了一种新的抑郁症动物模型。当任务的难度增加时，一些小鼠逐渐停止游泳，变得静止不动；这种反应表明无助状态。在这项研究中，我们研究了无助小鼠抑郁样表型的关键机制。训练早期的逃避失败增加了无助小鼠的发生率。然而，训练阶段偶尔的成功逃脱会增加后续学习任务中的不动和认知障碍。另一方面，反复给予氟伏沙明24天后，无助小鼠齿状回BrdU阳性细胞数量显著增加，这一效果与行为改善平行。这一结果表明，在无助的小鼠中，海马神经发生的减少与强健和一致的行为异常有关。

We have developed a new animal model of depression by modifying the water maze learning task in mice. When the difficulty of the task is increased, some of the mice gradually cease to swim and become immobile; this response indicates a helpless state. In this research, we investigated a critical mechanism underlying depression-like phenotypes of the helpless mice. Escape failures at early stage of training increased occurrence of the helpless mice. However, occasional successful escape during the training phase enhanced immobility and cognitive impairments in subsequent learning task. On the other hand, repeated administration of fluvoxamine for 24 days caused a significant increase in the number of BrdU-positive cells in the dentate gyrus of the helpless mice, an effect which was paralleled by a behavioral improvement. This result suggests that the reduction of hippocampal neurogenesis is associated with robust and consistent behavioral abnormalities in the helpless mice.