Effect of Acute and Chronic Administration of Methylphenidate on Mitochondrial Respiratory Chain in the Brain of Young Rats

Abstract

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.

Crocin acts as a neuroprotective mediator against methylphenidate-induced neurobehavioral and neurochemical sequelae: Possible role of the CREB-BDNF signaling pathway

“…These outcomes are similar to prior findings, which showed MPH-induced lipid peroxidation in the brain ( Martins et al, 2006;Schmitz et al, 2012). According to these data, it appears that part of the damaging effects of MPH are mediated by mitochondrial dysfunction, and crocin may play a role in moderating this process (Fagundes et al, 2010). Moreover, it has been indicated by prior work that crocin exerts neuroprotective properties by inhibiting the creation of free radicals in neurodegenerative diseases such as Alzheimer's disease (Hosseinzadeh et al, 2009;Khalili and Hamzeh, 2010;Rashedinia et al, 2015).…”

“…Our results showed that MPH (10 mg/kg) reduces the content of mitochondrial GSH, but increases levels of GSSG in hippocampal tissues. The conversion of GSH to GSSG by MPH is a main step that can start and trigger neurodegenerative signals in the brain (Martins et al, 2006;Fagundes et al, 2010), and this mechanism has damaging effects on the glutathione cycle and thus causes neural cell death ( Martins et al, 2006;Fagundes et al, 2010). Furthermore, we found that several doses of crocin, particularly 40 and 80 mg/kg, increase GSH content while decreasing GSSG levels in animals treated with MPH (10 mg/kg).…”

Methylphenidate treatment causes oxidative stress and alters energetic metabolism in an animal model of attention-deficit hyperactivity disorder

“…Recently, our group demonstrated that, after chronic administration of MPH in the adult rats, the complexes I, II, III and IV were inhibited in the hippocampus, prefrontal cortex, striatum and cerebral cortex (45) and there were not alterations in the oxidative parameters in the same structures listed above (46). Nevertheless, it is imperative to note that MPH treatment in these studies was derived from ‘healthy’ animals.…”

Methylphenidate effects in the young brain: friend or foe?

“…The results of this study revealed that mitochondrial respiratory chain complexes I, II, III, and IV were inhibited in the hippocampus, PFC, striatum, and cerebral cortex both after the single dose and after the chronic exposure (Fagundes et al, 2010b). The exact same treatment schedule was applied to young male Wistar rats (PND 25) and the results were different (Fagundes et al, 2010a). After the acute treatment, the results showed a reduction in the activity of complex I in the cerebellum and PFC and, after chronic treatment, the activities of complexes II and IV were increased in the young animals (Fagundes et al, 2010a).…”

“…The exact same treatment schedule was applied to young male Wistar rats (PND 25) and the results were different (Fagundes et al, 2010a). After the acute treatment, the results showed a reduction in the activity of complex I in the cerebellum and PFC and, after chronic treatment, the activities of complexes II and IV were increased in the young animals (Fagundes et al, 2010a).…”