Effects of methylphenidate: the cellular point of view
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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.
KeywordsMethylphenidate PC12 cells Synaptic Proteins Norepinephrine Transporter Neurotransmitter release Cell proliferation
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.
Conflict of interest
All other authors declare that they have no conflicts of interest.
- Ferris RM, Tang FL et al (1972) A comparison of the capacities of isomers of amphetamine, deoxypipradrol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther 181(3):407–416PubMedGoogle Scholar
- Schmidt A, Krieg J et al. (2009) Impact of drugs approved for treating ADHD on the cell survival and energy metabolism: an in vitro study in human neuronal and immune cells. J Psychopharmacol. doi: 10.1177/0269881109105563
- Vandesompele J, De Preter K et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):RESEARCH0034Google Scholar
- Volkow ND, Fowler JS et al. (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6(Suppl 1):S31–S43Google Scholar
- Wilens TE (2008) Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 28(3 Suppl 2):S46–S53Google Scholar