Nitric oxide synthase inhibition attenuates l -DOPA-induced dyskinesias in a rodent model of Parkinson's disease

• Published in: Neuroscience 2009-03, Vol.159 (3), p.927-935
• Main Authors: Padovan-Neto, F.E, Echeverry, M.B, Tumas, V, Del-Bel, E.A
• Format: Article
• Language: English
• Subjects: 6-hydroxydopamine; abnormal involuntary movements; Animals; Antiparkinson Agents - adverse effects; Antiparkinson Agents - therapeutic use; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; dyskinesia; Dyskinesia, Drug-Induced - drug therapy; Enzyme Inhibitors - therapeutic use; Fundamental and applied biological sciences. Psychology; Indazoles - therapeutic use; l-DOPA; Levodopa - adverse effects; Levodopa - therapeutic use; Male; Medical sciences; Motor Activity - drug effects; Neurology; Nitric Oxide Synthase - antagonists & inhibitors; nitric oxide synthase inhibitors; Nitroarginine - therapeutic use; Oxidopamine; Parkinson Disease - drug therapy; Rats; Rats, Wistar; Substantia Nigra - drug effects; Substantia Nigra - pathology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.01.034

Abstract 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.