We studied the effects of oral administration of Afobazole in a dose of 10 mg/kg for 5 days on depressive-like behavior of male C57BL/6 mice in the tail suspension test in comparison with amitriptyline (10 mg/kg) or fluoxetine (20 mg/kg) treatment. Afobazole produced an antidepressant effect similar to amitriptyline, but inferior to fluoxetine. The σ1 receptor antagonist BD-1047 in a dose of 5 mg/kg blocked the antidepressant effect of Afobazole, which indicates the involvement of σ1 receptors in the antidepressant effect of the drug.