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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 5
[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
Total Affiliations: 3
Document type: Journal article
Source: Neuropharmacology; v. 89, p. 87-99, FEB 2015.
Web of Science Citations: 18

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)

FAPESP's process: 09/08181-9 - Basal ganglia neuroplasticity: role of nitric oxide on Parkinsons Disease and L-Dopa-induced dyskinesias
Grantee:Fernando Eduardo Padovan Neto
Support type: Scholarships in Brazil - Doctorate