Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis-SC, Brazil.
Pharmacol Biochem Behav. 2012 Dec;103(2):204-11. doi: 10.1016/j.pbb.2012.08.016. Epub 2012 Aug 25.
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.
熊果酸是迷迭香中的一种三萜化合物，因其具有抗癌和抗氧化特性而被广泛研究。本研究采用两种抗抑郁药效预测实验，即悬尾实验（TST）和强迫游泳实验（FST），研究了这种植物中分离得到的熊果酸的抗抑郁样作用。此外，还研究了 TST 中多巴胺能系统在其抗抑郁样作用中的参与情况。熊果酸（0.01 和 0.1mg/kg，po）和氟西汀（10mg/kg，po）、丙咪嗪（1mg/kg，po）、安非他酮（10mg/kg，po）均可减少 TST 中的不动时间。熊果酸（0.1mg/kg，po）在 TST 中的作用可被预先给予小鼠 SCH23390（0.05mg/kg，sc，多巴胺 D1 受体拮抗剂）和舒必利（50mg/kg，ip，多巴胺 D2 受体拮抗剂）所阻断。给予亚有效剂量的熊果酸（0.001mg/kg，po）与亚有效剂量的 SKF38393（0.1mg/kg，sc，多巴胺 D1 受体激动剂）、阿扑吗啡（0.5μg/kg，ip，多巴胺 D2 受体选择性激动剂）或安非他酮（1mg/kg，ip，双重多巴胺/去甲肾上腺素摄取抑制剂）联合给药可减少 TST 中的不动时间，而与任一药物单独给药相比。熊果酸和多巴胺能药物单独或联合使用均不会引起运动和探索活动的显著改变。这些结果表明，熊果酸在 TST 中的抗抑郁样作用可能是通过与多巴胺能系统相互作用介导的，通过激活多巴胺 D1 和 D2 受体。
