Behavioral Despair during a Water Maze Learning Task in Mice

In the case of mice, when the difficulty of a water maze learning task is increased, some animals gradually cease to swim, abandon adaptive learning, and become immobile. We trained 99 male C57BL/6N mice in a pool containing a hidden platform. The pool was surrounded by white featureless walls, and almost all external cues were removed. On the eighth day of escape training, 36 inferior-learners exhibited behavioral despair. The predictive validity of the inferior-learners as a depression model was verified by testing their sensitivity to clinically efficacious antidepressants. The inferior-learners treated with a selective serotonin reuptake inhibitor (SSRI), fluvoxamine, or a serotonin noradrenaline reuptake inhibitor (SNRI), milnacipran, resumed swimming and adaptive learning. Because of facial similarities between inferior-learners and depressive patients and their sensitivity to antidepressant drugs, our experimental method is expected to be an effective tool in basic research on depression.