RESUMO
Methylphenidate is commonly used for the treatment of attention deficit/hyperactivity disorder. There are still few works regarding the effects of methylphenidate on brain energy metabolism. Thus, in the present study we evaluated the effect of chronic administration of methylphenidate on the activities of mitochondrial respiratory chain complexes I and III in the brain of young rats. The effect of acute administration of methylphenidate on mitochondrial respiratory chain complexes I, II, III and IV in the brain of young rats was also investigated. For acute administration, a single injection of methylphenidate was given to rats on postnatal day 25. For chronic administration, methylphenidate injections were given starting at postnatal day 25 once daily for 28 days. Our results showed that complexes I and III were not affected by chronic administration of methylphenidate. Moreover, the acute administration of methylphenidate decreased complex I activity in cerebellum and prefrontal cortex, whereas complexes II, III and IV were not altered.
Assuntos
Transporte de Elétrons/efeitos dos fármacos , Metilfenidato/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Complexo I de Transporte de Elétrons/efeitos dos fármacos , Complexo III da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Masculino , Metilfenidato/farmacologia , Mitocôndrias/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , RatosRESUMO
Methylphenidate (MPH) is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. It was previously demonstrated that MPH altered brain metabolic activity. Most cell energy is obtained through oxidative phosphorylation, in the mitochondrial respiratory chain. However, there are still few studies about MPH effects on the brain of adult rats. Thus, in the present study we evaluated the effect of acute or chronic administration of MPH on the activities of mitochondrial respiratory chain complexes I-IV in the brain of adult rats. For acute administration, a single injection of MPH was given to 60-day-old rats. For chronic administration, MPH injections were given to 60-day-old rats once daily for 28 days. Our results showed that complexes I, II, III and IV were inhibited after acute or chronic MPH administration in the hippocampus, prefrontal cortex, striatum and cerebral cortex. On the other hand, cerebellum was not affected.
Assuntos
Química Encefálica/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Transporte de Elétrons/efeitos dos fármacos , Metilfenidato/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Masculino , Mitocôndrias/enzimologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
AIMS: The high prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) and the increased therapeutic use of methylphenidate (MPH) raise some concerns regarding its long-term side effects and safety profile. Considering that MPH effects on brain metabolism are poorly known and that creatine kinase (CK) plays an important role in cell energy homeostasis, we evaluated CK activity in the brain of young and adult rats following acute (one injection) or chronic (28 days) administration of MPH. MAIN METHODS: MPH was acutely or chronically administered to young and adult rats. For acute administration, a single injection of MPH was given to rats on postnatal day (PD) 25 or PD 60, in the young and adult groups, respectively. For chronic administration, MPH injections were given to young rats starting at PD 25 once daily for 28 days (last injection at PD 53). In adult rats, the same regimen was performed starting at PD 60 (last injection at PD 88). CK activity was measured in brain homogenates. KEY FINDINGS: Our results showed that MPH acute administration increased the enzyme in prefrontal cortex, hippocampus, striatum and cerebral cortex, but not cerebellum of young and adult rats. Chronic administration of MPH also increased CK activity in these brain regions, as well as the cerebellum, in young and adult rats. The highest dose (10.0 mg/kg) presented more pronouncing effects. SIGNIFICANCE: The present findings suggest that acute or chronic exposure to MPH increased CK activity, an enzyme involved in energy homeostasis, in the brain of young and adult rats.
Assuntos
Envelhecimento/metabolismo , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Creatina Quinase/metabolismo , Metilfenidato/efeitos adversos , Animais , Encéfalo/enzimologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Esquema de Medicação , Masculino , Metilfenidato/administração & dosagem , Ratos , Ratos WistarRESUMO
Methylphenidate is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. Psychostimulants can cause long-lasting neurochemical and behavioral adaptations. The exact mechanisms underlying its therapeutic and adverse effects are still not well understood. In this context, it was previously demonstrated that methylphenidate altered brain metabolic activity, evaluated by glucose consumption. Most cell energy is obtained through oxidative phosphorylation, in the mitochondrial respiratory chain. Tissues with high energy demands, such as the brain, contain a large number of mitochondria. In this work, our aim was to measure the activities of mitochondrial respiratory chain complexes II and IV and succinate dehydrogenase in cerebellum, prefrontal cortex, hippocampus, striatum, and cerebral cortex of young rats (starting on 25th post-natal day and finishing on 53rd post-natal day) chronically treated with methylphenidate. Our results showed that mitochondrial respiratory chain enzymes activities were increased by chronic administration of this drug. Succinate dehydrogenase was activated in cerebellum, prefrontal cortex and striatum, but did not change in hippocampus and brain cortex. Complex II activity was increased in cerebellum and prefrontal cortex and was not affected in hippocampus, striatum and brain cortex. Finally, complex IV activity was increased in cerebellum, hippocampus, striatum and brain cortex, and was not affected in prefrontal cortex. These findings suggest that chronic exposure to methylphenidate in young rats increases mitochondrial enzymes involved in brain metabolism. Further research is being carried out in order to better understand the effects of this drug on developing nervous system and the potential consequences in adulthood resulting from early-life drug exposure.