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ADHD Attention Deficit and Hyperactivity Disorders

Erschienen in:

01.12.2010 | Original Article

Effects of methylphenidate: the cellular point of view

verfasst von: Jasmin Bartl, Pille Link, Corinna Schlosser, Manfred Gerlach, Angelika Schmitt, Susanne Walitza, Peter Riederer, Edna Grünblatt

Erschienen in: ADHD Attention Deficit and Hyperactivity Disorders | Ausgabe 4/2010

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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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Berridge CW, Devilbiss DM et al (2006) Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 60(10):1111–1120CrossRefPubMed

Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366(9481):237–248CrossRefPubMed

Easton N, Steward C et al (2007) Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal and synaptic vesicle accumulation and release of dopamine and noradrenaline in vitro in the rat brain. Neuropharmacology 52(2):405–414CrossRefPubMed

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):407–416PubMed

Gatley SJ, Pan D et al (1996) Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters. Life Sci 58(12):231–239CrossRefPubMed

Hahn MK, Steele A et al (2009) Novel and functional norepinephrine transporter protein variants identified in attention-deficit hyperactivity disorder. Neuropharmacology 57(7–8):694–701CrossRefPubMed

Han DD, Gu HH (2006) Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs. BMC Pharmacol 6:6CrossRefPubMed

Jaeger CB (1985) Immunocytochemical study of PC12 cells grafted to the brain of immature rats. Exp Brain Res 59(3):615–624CrossRefPubMed

Kadota T, Yamaai T et al (1996) Expression of dopamine transporter at the tips of growing neurites of PC12 cells. J Histochem Cytochem 44(9):989–996PubMed

Kim CH, Hahn MK et al (2006) A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder. Proc Natl Acad Sci USA 103(50):19164–19169CrossRefPubMed

Kuczenski R, Segal DS (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem 68(5):2032–2037CrossRefPubMed

Lagace DC, Yee JK et al (2006) Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psychiatry 60(10):1121–1130CrossRefPubMed

Ludolph AG, Schaz U et al (2006) Methylphenidate exerts no neurotoxic, but neuroprotective effects in vitro. J Neural Transm 113(12):1927–1934CrossRefPubMed

Riederer P, Reynolds GP (1981) Determination of a wide range of urinary amine metabolites using a simple high-performance liquid chromatographic technique. J Chromatogr 225(1):179–184CrossRefPubMed

Roden WH, Papke JB et al (2007) Stable RNA interference of synaptotagmin I in PC12 cells results in differential regulation of transmitter release. Am J Physiol Cell Physiol 293(6):C1742–C1752CrossRefPubMed

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

Shafer TJ, Atchison WD (1991) Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxicological studies. Neurotoxicology 12(3):473–492PubMed

Sung U, Blakely RD (2007) Calcium-dependent interactions of the human norepinephrine transporter with syntaxin 1A. Mol Cell Neurosci 34(2):251–260CrossRefPubMed

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):RESEARCH0034

Volkow ND, Fowler JS et al. (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6(Suppl 1):S31–S43

Volz TJ, Farnsworth SJ et al (2008) Methylphenidate-induced alterations in synaptic vesicle trafficking and activity. Ann N Y Acad Sci 1139:285–290CrossRefPubMed

Wall SC, Gu H et al (1995) Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 47(3):544–550PubMed

Wilens TE (2008) Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 28(3 Suppl 2):S46–S53

Zachor DA, Moore JF et al (2000) Cocaine inhibits NGF-induced PC12 cells differentiation through D(1)-type dopamine receptors. Brain Res 869(1–2):85–97CrossRefPubMed

Zhang J, Xu M (2006) Opposite regulation of cocaine-induced intracellular signaling and gene expression by dopamine D1 and D3 receptors. Ann N Y Acad Sci 1074:1–12CrossRefPubMed

Titel: Effects of methylphenidate: the cellular point of view
verfasst von: Jasmin Bartl
Pille Link
Corinna Schlosser
Manfred Gerlach
Angelika Schmitt
Susanne Walitza
Peter Riederer
Edna Grünblatt
Publikationsdatum: 01.12.2010
Verlag: Springer Vienna
Erschienen in: ADHD Attention Deficit and Hyperactivity Disorders / Ausgabe 4/2010
Print ISSN: 1866-6116
Elektronische ISSN: 1866-6647
DOI: https://doi.org/10.1007/s12402-010-0039-6

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