New behavioral animal model to study vulnerability factors for depression

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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.