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ABSTRACT: OBJECTIVE: To investigate the antidepressant-like effect of glycyrrhizin (glycyrrhizic acid ammonium) in mice. MATERIALS AND METHODS: Glycyrrhizin (1.5, 3.0 and 6.0 mg/kg, i.p.) was administered once daily for seven successive days to separate groups of young male Swiss albino mice. The immobility periods of control and treated mice were recorded in forced swim test (FST) and tail suspension test (TST). Effect of sulpiride (50 mg/kg, i.p.; a selective D2 receptor antagonist), prazosin (62.5 µg/kg, i.p.; an α1-adrenoceptor antagonist) and p-chlorophenylalanine (100 mg/kg, i.p.; an inhibitor of serotonin synthesis) on antidepressant-like effect of glycyrrhizin in TST was also studied. The antidepressant-like effect of glycyrrhizin was compared to that of imipramine (15 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) administered for seven successive days. RESULTS: Glycyrrhizin produced significant antidepressant-like effect at a dose of 3.0 mg/kg administered for seven successive days, as indicated by reduction in the immobility times of mice in both FST and TST. Glycyrrhizin did not show significant effect on locomotor activity of mice. The efficacy of glycyrrhizin was found to be comparable to that of imipramine and fluoxetine. Sulpiride and prazosin significantly attenuated the glycyrrhizin-induced antidepressant-like effect in TST. On the other hand, p-chlorophenylalanine did not reverse antidepressant-like effect of glycyrrhizin. This suggests that the antidepressant-like effect of glycyrrhizin seems to be mediated by an increase in brain norepinephrine and dopamine, but not by an increase in serotonin. CONCLUSION: The results of the present study indicate the involvement of adrenergic and dopaminergic systems in the antidepressant-like effect of glycyrrhizin.