Nitric oxide synthase inhibition attenuates L-DOPA-induced dyskinesias in a rodent model of Parkinson's disease.
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.
Padovan-Neto
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Department of Neurology, Psychiatry and Medical Psychology, School of Medicine, Campus USP, Av. Bandeirantes 13400, 14049-900, Ribeirão Preto, SP, Brazil.
Echeverry
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MB
Tumas
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Del-Bel
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EA
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000627:therapeutic use; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
D000978:Antiparkinson Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D019335:Nitroarginine; D007980:Levodopa; D016627:Oxidopamine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole