Evidence of methylphenidate effect on mitochondria, redox homeostasis, and inflammatory aspects: Insights from animal studies

Methylphenidate (MPH) is a central nervous system (CNS) stimulant known for its effectiveness in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), a neuropsychiatric condition that has a high incidence in childhood and affects behavior and cognition. However, the increase in its use among individuals who do not present all the diagnostic criteria for ADHD has become a serious public health problem since the neurological and psychiatric consequences of this unrestricted use are not widely known. In addition, since childhood is a critical period for the maturation of the CNS, the high prescription of MPH for preschool children also raises several concerns. This review brings new perspectives on how MPH (in different doses, routes of administration and ages) affects the CNS, focusing on animal studies that evaluated changes in mitochondrial (bioenergetics), redox balance and apoptosis, as well as inflammatory parameters. MPH alters brain energy homeostasis, increasing glucose consumption and impairing the activity of enzymes in the Krebs cycle and electron transport chain, as well as ATP levels and Na+, K+-ATPase activity. MPH induces oxidative stress, increasing the levels of reactive oxygen and nitrogen species and altering enzymatic and non-enzymatic antioxidant defenses, which, consequently, is related to damage to proteins, lipids, and DNA. Among the harmful effects of MPH, studies also demonstrate its ability to induce inflammation as well as alter the apoptosis pathway. It is important to highlight that age, treatment time, administration route, and dose are factors that can influence MPH effects. However, young animals seem to be more susceptible to damage caused by MPH. It is possible that changes in mitochondrial function and markers of status oxidative, apoptosis and inflammation may be exerting important mechanisms associated with MPH toxicity and, therefore, the unrestricted use of this drug can cause brain damage.

Automated summary

Methylphenidate (MPH) is effective in treating Attention Deficit Hyperactivity Disorder (ADHD), but its unrestricted use can have neurological and psychiatric consequences. Animal studies show that MPH alters brain energy homeostasis, induces oxidative stress, causes inflammation, and alters the apoptosis pathway. Age, treatment time, administration route, and dose are important factors that influence the effects of MPH.