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

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.

Oxidative and nitrosative stress in ADHD: possible causes and the potential of antioxidant-targeted therapies

“…Findings are inconsistent with reports of positive (Schmidt et al 2010;Schmitz et al 2012a), adverse (Comim et al 2014;Martins et al 2006;Schmitz et al 2012b) and null effects (Cöngöloğlu et al 2006;Gomes et al 2008). This makes conclusions about the impact of such medications on O&NS difficult as results seem to be influenced by treatment duration (acute versus chronic), age of population (young versus adult), brain region examined, biomarker measured, and dosage of drug administered.…”

Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats

“…MPH was dissolved in 0.9 % saline solution and injected at a volume of 1 ml/100 g of body weight. Control group received equivalent volume of saline solution [36,37]. This dose and route of administration were selected because they mimic the therapeutic doses in terms of magnitude of neurochemical and behavioral effects [38].…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Most important in this regard is methylphenidate. As with cocaine, there are reports of increased oxidative stress and lipid peroxidation in certain brain regions after methylphenidate, whereas long-term depletion of monoamine levels is not observed (Yuan et al, 1997;Schmitz et al, 2012;Comim et al, 2014). Analogous with cocaine, methylphenidate also protects against toxicity of amphetamines, and it has been suggested it may also be protective against the neurodegenerative processes occurring in Parkinson's disease (Volz, 2008).…”