Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: Evidence for the involvement of monoaminergic systems

The relationship between depression and monoaminergic systems has been hypothesized for many years. In this study, we have investigated the possible antidepressant-like effect of scopoletin, a coumarin from Polygala sabulosa in the tail suspension test and forced swimming test. Moreover, the ability of scopoletin to reverse the depression-like behavior in the forced swimming test induced by immobility stress in mice was evaluated. Scopoletin reduced the immobility time in the tail suspension test (10–100 mg/kg, p.o.), but not in the forced swimming test. Fluoxetine (positive control) decreased the immobility time in the forced swimming and tail suspension tests (20 mg/kg, p.o. and 10 mg/kg. p.o., respectively). Immobility stress caused an increase in the immobility time in the forced swimming test (depression-like behavior), which was reversed by scopoletin (1–100 mg/kg, p.o.) and fluoxetine (10 mg/kg, p.o.). Scopoletin produced no psychostimulant effect in the open-field test. The pretreatment of mice with ketanserin (5 mg/kg, i.p., a preferential 5-HT 2A receptor antagonist), prazosin (1 mg/kg, i.p., an α 1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α 2-adrenoceptor antagonist), haloperidol (0.2 mg/kg, i.p., a dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D 1 receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D 2 receptor antagonist), but not WAY100635 (0.1 mg/kg, s.c., a selective 5-HT 1A receptor antagonist) prevented the antidepressant-like effect of scopoletin (10 mg/kg, p.o.) in the tail suspension test. The results indicate that its antidepressant-like effect is dependent on the serotonergic (5-HT 2A receptors), noradrenergic (α 1- and α 2-adrenoceptors) and dopaminergic (dopamine D 1 and D 2 receptors) systems.