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

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs

“…The first reason we propose is related to possible changes in DA receptors that modulate the response to MPH: in murine models, D1 and D2 receptors were suggested to play a synergistic role in the sensitization to the therapeutic effects exerted by MPH [ 74 ]; thereby, a significant increase in S100B values in the first months after therapy could be linked to MPH-induced overactivation of D2 receptors, given the capacity of S100B to bind this receptor and potentiate its activity [ 75 , 76 ]. A second explanation could be associated with the excess of DA possibly generated by MPH, which has been reported to lead to reactive oxygen species (ROS) production and depletion of the antioxidant glutathione in preclinical studies [ 77 , 78 , 79 ]. According to this, MPH administration might have originated an initial inflammatory response involving S100B [ 24 , 25 , 26 , 27 ] in our patients as a consequence of the increase in DA levels.…”

Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats

“…Altogether, these result may suggest long-term consequences of MPH on dopamine neurotransmission. Additional studies have also witnessed long-term consequence of MPH on brain metabolism [ 63 ], inflammation [ 64 ] and peripheral hemostasis [ 65 ]. Our results need to be studied further in order to determine the role of D1- or D2-like receptors after chronic exposure to MPH.…”

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo: Part 2: Oxidative Stress and Immunological Modulation

“…According to a study of Gomes et al it was observed that MPH alters SOD activity in different brain structures like the cerebellum, prefrontal cortex in an adult rat model emphasizing that the effect of MPH on redox homeostasis is dependent on specific brain regions (Comim et al, 2014). Moreover, in an animal model of ADHD it was demonstrated that MPH causes lipid peroxidation in the brain and altered antioxidant enzymatic activities, hereby confirming that MPH can trigger oxidative stress even in an ADHD model (Comim et al, 2014;Foschiera et al, 2022). In addition to alternating activities of antioxidant enzymes in the brain, another animal study demonstrated that intraperitoneal administration of MPH (20 mg/kg) resulted in reduced levels of GSH in isolated hippocampal mitochondria (Foschiera et al, 2022;Motaghinejad et al, 2016).…”

“…Furthermore, over the last years interest in preclinical studies investigating the role of MPH on neurological functioning is growing. Evidence from these studies suggest that (mis)use of MPH is associated with redox and energy metabolism changes in the CNS (Foschiera et al, 2022). According to a study of Gomes et al it was observed that MPH alters SOD activity in different brain structures like the cerebellum, prefrontal cortex in an adult rat model emphasizing that the effect of MPH on redox homeostasis is dependent on specific brain regions (Comim et al, 2014).…”