Padovan-Neto F E, Echeverry M B, Tumas V, Del-Bel E A
Department of Neurology, Psychiatry and Medical Psychology, School of Medicine, Campus USP, Av. Bandeirantes 13400, 14049-900, Ribeirão Preto, SP, Brazil.
Neuroscience. 2009 Mar 31;159(3):927-35. doi: 10.1016/j.neuroscience.2009.01.034. Epub 2009 Jan 23.
Chronic L-DOPA pharmacotherapy in Parkinson's disease is often accompanied by the development of abnormal and excessive movements known as L-DOPA-induced dyskinesia. Rats with 6-hydroxydopamine lesion of dopaminergic neurons chronically treated with L-DOPA develop a rodent analog of this dyskinesia characterized by severe axial, limb, locomotor and orofacial abnormal involuntary movements. While the mechanisms by which these effects occur are not clear, they may involve the nitric oxide system. In the present study we investigate if nitric oxide synthase inhibitors can prevent dyskinesias induced by repeated administration of L-DOPA in rats with unilateral 6-hydroxydopamine lesion. Chronic L-DOPA (high fixed dose, 100 mg/kg; low escalating dose, 10-30 mg/kg) treatment induced progressive dyskinesia changes. Two nitric oxide synthase inhibitors, 7-nitroindazole (1-30 mg/kg) and NG-nitro-L-arginine (50 mg/kg), given 30 min before L-DOPA, attenuate dyskinesia. 7-Nitroindazolee also improved motor performance of these animals in the rota-rod test. These results suggest the possibility that nitric oxide synthase inhibitors may be useful to treat L-DOPA-induced dyskinesia.
帕金森病的慢性左旋多巴药物治疗常伴随着异常和过度运动的出现，即左旋多巴诱导的运动障碍。用左旋多巴长期治疗的多巴胺能神经元6-羟基多巴胺损伤大鼠会出现这种运动障碍的啮齿动物类似物，其特征为严重的轴向、肢体、运动和口面部异常不自主运动。虽然这些效应发生的机制尚不清楚，但可能涉及一氧化氮系统。在本研究中，我们调查一氧化氮合酶抑制剂是否能预防单侧6-羟基多巴胺损伤大鼠反复给予左旋多巴诱导的运动障碍。慢性左旋多巴（高固定剂量，100mg/kg；低递增剂量，10-30mg/kg）治疗引起进行性运动障碍变化。在给予左旋多巴前30分钟给予两种一氧化氮合酶抑制剂，7-硝基吲唑（1-30mg/kg）和NG-硝基-L-精氨酸（50mg/kg），可减轻运动障碍。7-硝基吲唑还改善了这些动物在转棒试验中的运动表现。这些结果表明一氧化氮合酶抑制剂可能对治疗左旋多巴诱导的运动障碍有用。
