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Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats

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Abstract

The use of psychostimulant methylphenidate has increased in recent years for the treatment of attention-deficit hyperactivity disorder in children and adolescents. However, the behavioral and neurochemical changes promoted by its use are not yet fully understood, particularly when used for a prolonged period during stages of brain development. Thus, the aim of this study was to determine some parameters of oxidative stress in encephalic structures of juvenile rats subjected to chronic methylphenidate treatment. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Two hours after the last injection, animals were euthanized and the encephalic structures obtained for determination of oxidative stress parameters. Results showed that methylphenidate administration increased the activities of superoxide dismutase and catalase, but did not alter the levels of reactive species, thiobarbituric acid reactive substances levels and sulfhydryl group in cerebellum of rats. In striatum and hippocampus, the methylphenidate-treated rats presented a decrease in the levels of reactive species and thiobarbituric acid reactive substances, but did not present changes in the sulfhydryl groups levels. In prefrontal cortex, methylphenidate promoted an increase in reactive species formation, SOD/CAT ratio, and increased the lipid peroxidation and protein damage. These findings suggest that the encephalic structures respond differently to methylphenidate treatment, at least, when administered chronically to young rats. Notably, the prefrontal cortex of juvenile rats showed greater sensitivity to oxidative effects promoted by methylphenidate in relation to other encephalic structures analyzed.

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Acknowledgments

This work was supported in part by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil).

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  1. Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil

    Felipe Schmitz, Emilene B. S. Scherer, Fernanda R. Machado, Aline A. da Cunha, Bárbara Tagliari, Carlos A. Netto & Angela T. S. Wyse

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  1. Felipe Schmitz
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  2. Emilene B. S. Scherer
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  3. Fernanda R. Machado
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  4. Aline A. da Cunha
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  5. Bárbara Tagliari
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  7. Angela T. S. Wyse
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Correspondence to Angela T. S. Wyse.

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Schmitz, F., Scherer, E.B.S., Machado, F.R. et al. Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats. Metab Brain Dis 27, 605–612 (2012). https://doi.org/10.1007/s11011-012-9335-5

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