Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats.
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.
Fagundes
Ana O
AO
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Rezin
Gislaine T
GT
Zanette
Francine
F
Grandi
Eliane
E
Assis
Lara C
LC
Dal-Pizzol
Felipe
F
Quevedo
João
J
Streck
Emilio L
EL
D000818:Animals; D001921:Brain / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D045222:Electron Transport Chain Complex Proteins; D008774:Methylphenidate