Abstract
The psychostimulant methylphenidate (MPH) is the first choice of treatment in attention-deficit hyperactivity disorder and is based mainly on inhibition of dopamine transporter (DAT). Nonetheless, the complete cellular effects of MPH are still unknown. We attempted to determine whether MPH influences neurotransmitter levels, synaptic gene expression, and cell proliferation in a dose-dependent manner in rat pheochromocytoma cells (PC12) lacking DAT. PC12 were treated in a dose-dependent manner with MPH. Gene expression level of synaptotagmin (Syt) 1 and 4, syntaxin 1a (Stx1a), and synaptic vesicle glycoprotein 2C (SV2C) was measured using quantitative real-time RT-PCR. Different Neurotransmitter release was measured using high-performance liquid chromatography (HPLC). Differences in cell proliferation were evaluated via BrdU incorporation. Treatment with low-dose MPH (1–100 nM) altered intra-/extracellular neurotransmitter levels, down-regulated all investigated genes as well as enhanced cell proliferation significantly. These data point to diverse effects of MPH on cell metabolism independent of inhibiting DAT.
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Acknowledgments
The authors express their appreciation for the funding that was provided by the “Deutsche Forschungsgemeinschaft (DFG)” in the “Klinische Forschergruppe Aufmerksamkeitsdefizit-/Hyperaktivitätssyndrom (ADHS)” KFO-125 http://www.uni-wuerzburg.de/nervenklinik/psychobiologie/kfg/index.html. We would like to thank Dr. Silvia Mandel for the generous gift of the PC12 cells. We would also like to add a special thanks to Mrs. Gabriela Ortega, Ms Miryame Hofmann and Mr. Rainer Burger for their excellent technical work and help. Funding for this study was provided by “Deutsche Forschungsgemeinschaft (DFG)” Grant KFO-125; the DFG had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
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Bartl, J., Link, P., Schlosser, C. et al. Effects of methylphenidate: the cellular point of view. ADHD Atten Def Hyp Disord 2, 225–232 (2010). https://doi.org/10.1007/s12402-010-0039-6
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DOI: https://doi.org/10.1007/s12402-010-0039-6