Bertaina-Anglade Valerie, La Rochelle Christophe Drieu, Scheller Dieter K A
Biotrial, Rennes, France.
Eur J Pharmacol. 2006 Oct 24;548(1-3):106-14. doi: 10.1016/j.ejphar.2006.07.022. Epub 2006 Jul 22.
Limited clinical data are available on the use of dopamine agonists for the control of motor function and also for the treatment of depression. This study was performed to evaluate the potential effects of the dopamine receptor agonist rotigotine in rat models of anxiety and depression. After repeated administration at doses of 0.05, 0.5, 1, and 5 mg/kg, rotigotine increased spontaneous motor activity at the 5 mg/kg dose after 3-5 days of treatment. At lower doses, the drug had no effect on locomotor activity. After a single administration, rotigotine had no anxiolytic activity in rats during the elevated plus-maze test or the Geller-Seifter conflict test. In the behavioral despair test (also known as the forced swim test), the 5 mg/kg dose of rotigotine enhanced the mobility of rats. Rotigotine (0.5, 1, and 5 mg/kg/day for 5 days) reversed the active avoidance deficit of helpless rats in the learned helplessness test, as shown by a significant decrease in escape failures after 3 to 4 days (0.5 mg/kg/day), 5 days (1 mg/kg/day), and 3 to 5 days (5 mg/kg/day) of treatment. During open-field testing of rats subjected to olfactory bulbectomy and given a 14-day schedule of rotigotine (0.3 mg/kg every 2 days), hyperactivity reversed according to a U-shaped dose-response curve. These results suggest that rotigotine may have antidepressant properties at doses of 1 mg/kg and lower. Potential effects at doses of 5 mg/kg and higher may be masked by an effect of the compound whereby general locomotor activity is enhanced.
关于使用多巴胺激动剂来控制运动功能以及治疗抑郁症的临床数据有限。本研究旨在评估多巴胺受体激动剂罗替戈汀在焦虑和抑郁大鼠模型中的潜在作用。以0.05、0.5、1和5mg/kg的剂量重复给药后，罗替戈汀在治疗3 - 5天后，5mg/kg剂量可增加自发运动活性。在较低剂量时，该药物对运动活性无影响。单次给药后，在高架十字迷宫试验或盖勒 - 西弗冲突试验中，罗替戈汀对大鼠没有抗焦虑活性。在行为绝望试验（也称为强迫游泳试验）中，5mg/kg剂量的罗替戈汀可增强大鼠的活动能力。罗替戈汀（0.5、1和5mg/kg/天，持续5天）在习得性无助试验中逆转了无助大鼠的主动回避缺陷，表现为在治疗3至4天（0.5mg/kg/天）、5天（1mg/kg/天）和3至5天（5mg/kg/天）后逃避失败显著减少。在对接受嗅球切除的大鼠进行旷场试验，并给予14天的罗替戈汀给药方案（每2天0.3mg/kg）时，多动现象根据U形剂量反应曲线得到逆转。这些结果表明，罗替戈汀在1mg/kg及更低剂量时可能具有抗抑郁特性。在5mg/kg及更高剂量时的潜在作用可能被该化合物增强一般运动活性的作用所掩盖。
