Anti-dyskinetic effect of the neuronal nitric oxide synthase inhibitor is linked to decrease of FosB/DeltaFosB expression

NEUROSCIENCE LETTERS

卷:541

Article

Padovan-Neto, Fernando Eduardo^1,2  Ferreira, Nadia Rubia²  de Oliveira-Tavares, Danielle^1,2  de Aguiar, Daniele³  da Silva, Celia Aparecida^1,2  Raisman-Vozari, Rita⁴  Del Bel, Elaine^1,2 

[1] Univ Sao Paulo, Sch Med, Dept Behav Neurosci, BR-14040904 Ribeirao Preto, SP, Brazil

[2] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Morphol Physiol & Pathol, Nucl Apoio Pesquisa Neurociencia Aplicada NAPNA, BR-14040904 Ribeirao Preto, SP, Brazil

[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Pharmacol, BR-31270910 Belo Horizonte, MG, Brazil

[4] Univ Paris 06, CNRS, Fac Med, INSERM,CRICM,UMR975,UMR 7225, Paris, France

关键词: 6-Hydroxydopamine;    L-DOPA;    Abnormal involuntary movements;    Nitric oxide;    FosB/Delta FosB;    7-Nitroindazole;    Dyskinesia;   

DOI  :  10.1016/j.neulet.2013.02.015

来源: Elsevier

【 摘 要 】

Rodents with lesion of dopaminergic pathway when receiving repeated L-3,4-dihydroxiphenylalanine (L-DOPA) treatment develop abnormal involuntary movements called dyskinesia. We demonstrated that nitric oxide synthase (NOS) inhibitors mitigate L-DOPA-induced dyskinesia in rodents. The aim of the present study was to verify if the in vivo preferential neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI) affect the expression of the transcription factor FosB/Delta FosB in the lesioned striatum, an indicator of neuronal activity associated with dyskinesia. Male Wistar rats with unilateral microinjection (medial forebrain bundle) of either the neurotoxin 6-hydroxidopamine (6-OHDA; n = 4-6/group) or saline (sham; n=6/group) were provided with L-DOPA (30 mg/kg plus benserazide 7.5 mg/kg/day, oral gavage), once a day during 22 days. 6-OHDA-lesioned animals developed abnormal involuntary movements (AIMs) classified as axial, limb, orofacial and locomotive dyskinesia and presented FosB/Delta FosB increase in the dopamine-depleted striatum. Administration of 7-NI (30 mg/kg, i.p.), 30 min prior to L-DOPA reduced the severity of AlMs (approximate to 65% for axial, limb and orofacial and 74% for locomotive AIMs scores), without interfering with the rotarod performance. Simultaneously, 7-NI attenuated the expression of FosB/Delta FosB in dopamine-depleted striatum (approximate to 65% in medial and approximate to 54% in lateral striatum, bregma 0.48 mm). FosB/Delta FosB expression in lateral striatum was correlated with L-DOPA-induced dyskinesia. The findings described here corroborate a new approach to the management of L-DOPA-therapy in Parkinson's disease (PD) treatment. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved.

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