Our findings demonstrated that the onset of depression-like behavior is attributable not to TD but to chronic stress, whereas TD triggered the impairment of cognitive function, and that regular exercise, whether moderate or intense, prevents depression-like behavior concomitantly with an improvement of hippocampal neurogenesis and an increase of hippocampal noradrenaline, despite the recovery of brain 5-HT. This evidence concerns the gene HTR5A and depressive disorder.