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Provedor de dados: |
BJMBR
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País: |
Brazil
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Título: |
Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats
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Autores: |
Novaretti,N.
Padovan-Neto,F.E.
Tumas,V.
da-Silva,C.A.
Del Bel,E.A.
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Data: |
2010-11-01
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Ano: |
2010
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Palavras-chave: |
Nitric oxide
Nitric oxide synthase
Parkinson’s disease
L-DOPA
Dyskinesia
DOPA priming
7-Nitroindazole
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Resumo: |
7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.
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Tipo: |
Info:eu-repo/semantics/article
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Idioma: |
Inglês
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Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001100006
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Editor: |
Associação Brasileira de Divulgação Científica
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Relação: |
10.1590/S0100-879X2010007500111
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Formato: |
text/html
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Fonte: |
Brazilian Journal of Medical and Biological Research v.43 n.11 2010
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Direitos: |
info:eu-repo/semantics/openAccess
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