Effect of antidepressant on behavior and central catecholamine were investigated in depression-model rats produced by long-term forced running stress. Changes in the spontaneous running activity and the concentration and turnover of catecholamine were examined in non-stressed rats injected with saline and depression-model rats injected with saline, imipramine and MOD-20 (a candidate for a tetracyclic antidepressant). Running activity was significantly restored by injection of imipramine and MOD-20. In depression-model rats, the concentrations of central catecholamine increased in the cell bodies and nerve terminals of the ascending noradrenaline system, and turnover rates of the catecholamine decreased in the terminal region. The increased concentrations were returned to the non-stressed level after injection of the drugs. However, decreased turnover rates were not recovered after the injection. These results suggested that MOD-20 was a potent antidepressant and the therapeutic efficacy of antidepressants might be due to the restoration of catecholamine concentrations.