Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: Evidence for the involvement of the dopaminergic system

Ursolic acid, a constituent from Rosmarinus officinalis, is a triterpenoid compound which has been extensively known for its anticancer and antioxidant properties. In the present study, we investigated the antidepressant-like effect of ursolic acid isolated from this plant in two predictive tests of antidepressant property, the tail suspension test (TST) and the forced swimming test (FST) in mice. Furthermore, the involvement of dopaminergic system in its antidepressant-like effect was investigated in the TST. Ursolic acid reduced the immobility time in the TST (0.01 and 0.1mg/kg, p.o.) and in the FST (10mg/kg, p.o.), similar to fluoxetine (10mg/kg, p.o.), imipramine (1mg/kg, p.o.) and bupropion (10mg/kg, p.o.). The effect of ursolic acid (0.1mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with SCH23390 (0.05mg/kg, s.c., a dopamine D(1) receptor antagonist) and sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist). The administration of a sub-effective dose of ursolic acid (0.001mg/kg, p.o.) in combination with sub-effective doses of SKF38393 (0.1mg/kg, s.c., a dopamine D(1) receptor agonist), apomorphine (0.5μg/kg, i.p., a preferential dopamine D(2) receptor agonist) or bupropion (1mg/kg, i.p., a dual dopamine/noradrenaline reuptake inhibitor) reduced the immobility time in the TST as compared with either drug alone. Ursolic acid and dopaminergic agents alone or in combination did not cause significant alterations in the locomotor and exploratory activities. These results indicate that the antidepressant-like effect of ursolic acid in the TST is likely mediated by an interaction with the dopaminergic system, through the activation of dopamine D(1) and D(2) receptors.