Inhibition of Mitochondrial Respiratory Chain in the Brain of Adult Rats After Acute and Chronic Administration of Methylphenidate

Abstract

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.

Attention Deficit Hyperactivity Disorder and oxidative stress: A short term follow up study

“…Türkbay et al (2009 reported that chronic administration of methylphenidate induces lipid peroxidation in the young rats' striatum. In two different studies conducted by Fagundes et al (2007Fagundes et al ( , 2010, it has been shown that chronic methylphenidate exposure affected different activities in the brains of young and adult rats-while increasing mitochondrial respiratory chain enzymes in young rats' brains, it reduced them in adult brains. Andreazza et al (2007) has shown that methylphenidate led to central (in cells of the striatum and hippocampus tıssues of the brain) and peripheral (blood leukocytes) early DNA damage in rats.…”

Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD)

“…Furthermore, dysregulation of the expression of this gene has been implicated in some neuropsychiatric disorders such as bipolar disorder [55]. A previous study reported inhibition of mitochondrial respiratory chain complex III in the striatum as well as other brain regions of adult Wistar rats exposed to chronic (28 days) treatment of methylphenidate [56]. Downregulation of mitochondrial respiratory complex III (as well that of other complexes) has been viewed as a compensatory response in order to maintain energy homeostasis through enhancement of other metabolic systems [56].…”

“…A previous study reported inhibition of mitochondrial respiratory chain complex III in the striatum as well as other brain regions of adult Wistar rats exposed to chronic (28 days) treatment of methylphenidate [56]. Downregulation of mitochondrial respiratory complex III (as well that of other complexes) has been viewed as a compensatory response in order to maintain energy homeostasis through enhancement of other metabolic systems [56]. Alternatively, it has been assumed to result from neurotoxic effects of methylphenidate via the generation of ROS [56].…”

“…Downregulation of mitochondrial respiratory complex III (as well that of other complexes) has been viewed as a compensatory response in order to maintain energy homeostasis through enhancement of other metabolic systems [56]. Alternatively, it has been assumed to result from neurotoxic effects of methylphenidate via the generation of ROS [56]. Further studies are required to examine this point in detail.…”

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

“…Fagundes et al [69] verified that complexes I, II, III and IV were inhibited in brain of adult rats by MPH acute administration. In addition, MPH increases central and peripheral indexes of early DNA damage in young and adult rats [70].…”