ObjectiveMethylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine.MethodsYoung male Wistar rats were administered MPD (1, 2, 5, or 10 mg/kg) once a day or an intraperitoneal injection of saline for 28 days (chronic treatment) or for 1 day (acute treatment). Two hours after the last administration the animals were decapitated and their striatum was dissected.ResultsIn this work, we show that continued treatment with MPD is capable of modifying the levels of phosphorylation of proteins JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2). Whereas the level of phosphorylation of protein ERK increased significantly, that of proteins JNK1/2 diminished.ConclusionThe alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect.