title: Effects of methylphenidate: the cellular point of view.
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.
authors: Clinical Neurochemistry Laboratory, Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Würzburg, Germany.
authors: Jasmin
authors: J
authors: Bartl
authors: Pille
authors: P
authors: Link
authors: Corinna
authors: C
authors: Schlosser
authors: Manfred
authors: M
authors: Gerlach
authors: Angelika
authors: A
authors: Schmitt
authors: Susanne
authors: S
authors: Walitza
authors: Peter
authors: P
authors: Riederer
authors: Edna
authors: E
authors: Grünblatt
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008774:Methylphenidate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018377:Neurotransmitter Agents / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D050863:Synaptotagmin I / Q000096:biosynthesis; D050857:Synaptotagmins / Q000096:biosynthesis; D050827:Syntaxin 1 / Q000096:biosynthesis
chemical_list: D000697:Central Nervous System Stimulants; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C403704:SV2C protein, rat; C494213:Stx1a protein, rat; D050863:Synaptotagmin I; D050827:Syntaxin 1; C494312:Syt1 protein, rat; C494294:Syt4 protein, rat; D050857:Synaptotagmins; D008774:Methylphenidate