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Methylphenidate treatment affects mitogen-activated protein kinase activation in the striatum of young rats
Clarissa M Comim1, Josimar G Pereira1, Sandro J Ribeiro1
11 Laboratory of Neurosciences and National Institute for Translational Medicine (INCT-TM), Postgradute Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Objective:
Methylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine.
Methods:
Young 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.
Results:
In 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.
Conclusion:
The alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect.
Insights
Methylphenidate (MPD) alters protein phosphorylation in rat brains, impacting JNK1/2 and ERK1/2 signaling pathways. This suggests a molecular mechanism for MPD
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Methylphenidate (MPD) is a central nervous system stimulant used to treat attention deficit/hyperactivity disorder (ADHD).
- Its therapeutic effects are primarily linked to dopamine reuptake inhibition.
- The precise molecular mechanisms underlying MPD's action require further elucidation.
Purpose of the Study:
- To investigate the effects of chronic and acute methylphenidate administration on protein phosphorylation in the rat striatum.
- To identify specific signaling pathways modulated by MPD treatment.
Main Methods:
- Young male Wistar rats received daily intraperitoneal injections of MPD (1, 2, 5, or 10 mg/kg) or saline for 28 days (chronic) or 1 day (acute).
- Striatal tissue was collected 2 hours after the final administration.
- Levels of phosphorylated JNK1/2 and ERK1/2 were analyzed.
Main Results:
- Chronic MPD treatment significantly altered the phosphorylation levels of JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2).
- Specifically, ERK1/2 phosphorylation increased, while JNK1/2 phosphorylation decreased.
- Acute treatment effects were not detailed in the abstract.
Conclusions:
- Alterations in mitogen-activated protein kinase (MAPK) signaling, including JNK and ERK pathways, represent a potential molecular mechanism for MPD's therapeutic effects.
- These findings contribute to understanding the neurobiological basis of ADHD pharmacotherapy.
