ORIGINAL ARTICLE Counteraction by Nitric Oxide Synthase Inhibitor of Neurochemical Alterations of Dopaminergic System in 6-OHDA-Lesioned Rats Under L-DOPA Treatment Elaine Del-Bel • Fernando Eduardo Padovan-Neto • Raphael Escorsim Szawka • Ce ´lia Aparecida da-Silva • Rita Raisman-Vozari • Janete Anselmo-Franci • Ange ´lica Caroline Romano-Dutra • Francisco Silveira Guimaraes Received: 5 June 2013 / Revised: 12 June 2013 / Accepted: 14 June 2013 Ó Springer Science+Business Media New York 2013 Abstract Nitric oxide synthase inhibitors reduce L-3, (Del-Bel et al., Cell Mol Neurobiol 25(2):371–392, 2005) 4-dihydroxyphenylalanine (L-DOPA)-induced abnormal motor effects subsequent to depletion of dopaminergic neurons in rodents and non-human primates. The present study used quantitative high-performance liquid chroma- tography to analyze, for the first time, dopamine metabo- lism in striatum of rats in order to elucidate the mechanism of action of the nitric oxide synthase inhibitors. Adult male Wistar rats received unilateral microinjection of saline (sham) or 6-hydroxydopamine (6-OHDA-lesioned) in the medial forebrain bundle. Past 3 weeks, rats were treated during 21 days with L-DOPA/benserazide (30 mg/kg/ 7.5 mg/kg, respectively, daily). On the 22nd day rats received an intraperitoneal (i.p.) injection of either vehicle or 7-nitroindazole, a preferential neuronal nitric oxide synthase inhibitor before L-DOPA. Abnormal involuntary movements and rotarod test were assessed as behavioral correlate of motor responses. Lesion intensity was evaluated through tyrosine hydroxylase immunohystochemical reaction. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and an extent of dopamine striatal tissue levels/dopamine metabolism were measured in the striatum. Lesion with 6-OHDA decreased dopamine, DOPAC, and DOPAC/ dopamine ratio in the lesioned striatum. L-DOPA treatment induced abnormal involuntary movements and increased DOPAC/dopamine ratio (nearly five times) in the lesioned striatum. L-DOPA-induced dyskinesia was mitigated by 7-nitroindazole, which also decreased dopamine turnover, dopamine and DOPAC levels. Our results revealed an almost two times increase in dopamine content in the non-lesioned striatum of 6-OHDA-lesioned rats. Reduction of striatal E. Del-Bel (&)  F. E. Padovan-Neto  C. A. da-Silva  J. Anselmo-Franci  A. C. Romano-Dutra Department of Morphology, Physiology and Pathology, School of Odontology, University of Sa ˜o Paulo, Campus Ribeira ˜o Preto, Av. Cafe ´ S/N, Ribeira ˜o Preto, SP 14040-904, Brazil e-mail: eadelbel@forp.usp.br E. Del-Bel  F. E. Padovan-Neto  C. A. da-Silva  F. S. Guimaraes Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil E. Del-Bel  F. E. Padovan-Neto Department of Behavioral Neurosciences, Medical School, University of Sa ˜o Paulo, Av. Bandeirantes 3900, Ribeira ˜o Preto, SP 14049-900, Brazil R. E. Szawka Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Anto ˆnio Carlos 6627, Belo Horizonte, MG 31270-910, Brazil R. Raisman-Vozari INSERM UMR-S 975, UPMC, CRICM, Experimental Therapeutics of Neurodegeneration, 75013 Paris, France R. Raisman-Vozari Faculte ´ de Me ´decine, Universite ´ Pierre & Marie Curie-Paris 6, CNRS, UMR 7225, 75013 Paris, France F. S. Guimaraes Department of Pharmacology, Medical School, University of Sa ˜o Paulo, Av. Bandeirantes 3900, Ribeira ˜o Preto, SP 14049-900, Brazil 123 Neurotox Res DOI 10.1007/s12640-013-9406-3