The present study investigated a possible antidepressant-like activity of bis selenide using two predictive tests for antidepressant effect on rodents: the forced swimming test (FST) and the tail suspension test (TST). Bis selenide (0.5-5 mg/kg, p.o.) decreased the immobility time in the mouse FST and TST. The anti-immobility effect of bis selenide (1 mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis), ketanserin (1 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), and ondasentron (1 mg/kg, i.p., a 5-HT(3) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a beta-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), or WAY 100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) did not block the antidepressant-like effect of bis selenide (1 mg/kg, p.o.) in the TST. Administration of bis selenide (0.1 mg/kg, p.o.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. Bis selenide did not alter Na(+) K(+) ATPase, MAO-A and MAO-B activities in whole brains of mice. Bis selenide produced an antidepressant-like effect in the mouse TST and FST, which may be related to the serotonergic system (5-HT(2A/2C) and 5-HT(3) receptors).