Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of L-DOPA-induced dyskinesia in 6-OHDA-lesioned rats

Texto completo
Autor(es):
Padovan-Neto, Fernando Eduardo [1, 2, 3] ; Cavalcanti-Kiwiatkoviski, Roberta [1] ; Gomes Carolino, Ruither Oliveira [1, 2] ; Anselmo-Franci, Janete [2] ; Del Bel, Elaine [1, 2, 3]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Odontol, Dept Morphol Physiol & Pathol, BR-14040904 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Behav Neurosci, BR-14040904 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14040904 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Neuropharmacology; v. 89, p. 87-99, FEB 2015.
Citações Web of Science: 18
Resumo

It is well known that nitric oxide (NO) interacts with dopamine (DA) within the striatal circuitry. The anti-dyskinetic properties of NO synthase (NOS) inhibitors demonstrate the importance of NO in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID). Here, we investigated the ability of a daily co-treatment of the preferential neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg), with L-DOPA (30 mg/kg) to counteract LID in unilaterally 6-OHDA-lesioned rats. We analyzed striatal nNOS-expressing interneurons, DA and 5-HT neurochemistry in the striatum and alterations of the Fos-B/AFosB expression in the corticostriatal, nigrostriatal and mesolimbic pathways. Prolonged administration of 7-NI inhibited the manifestation of chronic L-DOPA treatment-induced abnormal involuntary movements (AIMS). LID was associated with an up-regulation in the number of nNOS-expressing interneurons in the lateral but not medial striatum. nNOS inhibition reduced the number of nNOS-expressing interneurons. The anti-dyskinetic effects of 7-NI correlated with a reduction in DA and 5-HT turnover in the striatum. At postsynaptic striatal sites, 7-NI prevented L-DOPA-induced Fos-B/AFosB up-regulation in the motor cortex, nucleus accumbens and striatum. Finally, 7-NI blocked Fos-B/AFosB expression in nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive interneurons in the striatum. These results provide further evidence of the molecular mechanisms by which NOS-inhibiting compounds attenuate LID. The involvement of NO with DA and 5-HT neurochemistry may contribute to the understanding of this new, non-dopaminergic therapy for the management of LID. (C) 2014 Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 09/08181-9 - Neuroplasticidade nos núcleos da base: papel do óxido nítrico na Doença de Parkinson e nas discinesias induzidas pela L-Dopa
Beneficiário:Fernando Eduardo Padovan Neto
Linha de fomento: Bolsas no Brasil - Doutorado