Therefore, the present study aimed (i) to determine whether 1-, 4- and 8-week restraint stress could induce anxiety- and depression-like behaviors, and impairments of spatial learning, spatial memory, and novel object recognition in male rats; and (ii) to evaluate the effectiveness of venlafaxine, agomelatine, and voluntary wheel running exercise in the reversal of stress-induced sequelae as well as induction of BDNF protein expression in the hippocampus. The gene discussed is BDNF; the disease is Anxiety.