Effects of methylphenidate: the cellular point of view
Open accessAbstract
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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Cites
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., & Speleman, F. (2002) · Genome Biology · doi:10.1186/gb-2002-3-7-research0034 · Cited by 20,038 · see citing works
Attention-deficit hyperactivity disorder
Biederman, J., & Faraone, S. V. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66915-2 · Cited by 1,463 · see citing works
Kuczenski, R., & Segal, D. S. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68052032.x · Cited by 623 · see citing works
Berridge, C. W., Devilbiss, D. M., Andrzejewski, M. E., Arnsten, A. F. T., Kelley, A. E., Schmeichel, B., Hamilton, C., & Spencer, R. C. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.022 · Cited by 617 · see citing works
Han, D. D., & Gu, H. H. (2006) · BMC Pharmacology · doi:10.1186/1471-2210-6-6 · Cited by 419 · see citing works
Mechanism of action of methylphenidate: Insights from PET imaging studies
Volkow, N. D., Fowler, J. S., Wang, G., Ding, Y., & Gatley, S. J. (2002) · Journal of Attention Disorders · doi:10.1177/070674370200601s05 · Cited by 353 · see citing works
Ferris, R. M., Tang, F. L. M., & Maxwell, R. A. (1972) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29222-9 · Cited by 303 · see citing works
Wilens, T. E. (2008) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318173312f · Cited by 269 · cited 1× · see citing works
“…unknown, but there is immense evidence that ADHD has multiple aetiologies (e.g. genetic, environmental, neurobiological, and neurochemical) in which catecholamine dysfunction, including afferent dopaminergic and noradrenergic neurotransmission, has an important underlying feature (Wilens 2008).”
BackgroundShafer, T. J., & Atchison, W. D. (1991) · PubMed · Cited by 252 · see citing works
Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters
Gatley, S. J., Pan, D., Chen, R., Chaturvedi, G., & Ding, Y. ‐. (1996) · Life Sciences · doi:10.1016/0024-3205(96)00052-5 · Cited by 203 · see citing works
Wall, S. C., Gu, H., & Rudnick, G. (1995) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)08574-8 · Cited by 183 · see citing works
Kim, C.-H., Hahn, M. K., Joung, Y., Anderson, S., Steele, A., Mazei-Robinson, M. S., Gizer, I., Teicher, M. H., Cohen, B., Robertson, D., et al. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0510836103 · Cited by 152 · see citing works
Easton, N., Steward, C., Marshall, F., Fone, K., & Marsden, C. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.035 · Cited by 101 · see citing works
Expression of dopamine transporter at the tips of growing neurites of PC12 cells.
Kadota, T., Yamaai, T., Saito, Y., et al. (1996) · Journal of Histochemistry & Cytochemistry · doi:10.1177/44.9.8773564 · Cited by 95 · see citing works
Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis
Lagace, D. C., Yee, J. K., Bolaños, C. A., & Eisch, A. J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.009 · Cited by 79 · see citing works
Immunocytochemical study of PC12 cells grafted to the brain of immature rats
Jaeger, C. B. (1985) · Experimental Brain Research · doi:10.1007/bf00261353 · Cited by 57 · see citing works
Cocaine inhibits NGF-induced PC12 cells differentiation through D1-type dopamine receptors
Zachor, D. A., Moore, J. F., Brezausek, C. M., et al. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02355-6 · Cited by 50 · see citing works
Calcium-dependent interactions of the human norepinephrine transporter with syntaxin 1A
Sung, U., & Blakely, R. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.11.007 · Cited by 35 · see citing works
Methylphenidate exerts no neurotoxic, but neuroprotective effects in vitro
Ludolph, A. G., Schaz, U., Storch, A., Liebau, S., Fegert, J. M., & Boeckers, T. M. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0487-5 · Cited by 33 · see citing works
Methylphenidate‐Induced Alterations in Synaptic Vesicle Trafficking and Activity
Volz, T. J., Farnsworth, S. J., Hanson, G. R., et al. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1432.012 · Cited by 31 · see citing works
Zhang, J., & Xu, M. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1369.001 · Cited by 24 · see citing works
Hahn, M. K., Steele, A., Couch, R. S., Stein, M. A., & Krueger, J. J. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.08.002 · Cited by 24 · see citing works
Schmidt, A., Krieg, J., Clement, H., Gebhardt, S., Schulz, E., & Heiser, P. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109105563 · Cited by 13 · see citing works
Riederer, P., & Reynolds, G. P. (1981) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)80257-1 · Cited by 12 · see citing works
Self-citationRoden, W. H., Papke, J. B., Moore, J. M., et al. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00482.2006 · Cited by 12 · see citing works
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Faraone, S. V. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.02.001 · Cited by 631 · see citing works
The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance
Stout, K. A., Dunn, A. R., Hoffman, C., & Miller, G. W. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00351 · Cited by 112 · see citing works
- Authors
- Bartl, J., Link, P., Schlosser, C., Gerlach, M., Schmitt, A., Walitza, S., Riederer, P., & Grünblatt, E.
- Affiliations
- University of Würzburg (DE)
- University of Zurich (CH)
- Corresponding author
- Grünblatt, Edna
- Venue
- ADHD Attention Deficit and Hyperactivity Disorders
- Published
- 2010-11-10
- Volume
- 2
- Issue
- 4
- Pages
- 225-232
- ISSN
- 1866-6116 (ISSN-L)
- 1866-6647
- OpenAlex
- W1965892703
- Cited by
- 29
- References
- 25
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- ADHD Attention Deficit and Hyperactivity Disorders (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- methylphenidate, dopamine transporter, attention deficit hyperactivity disorder, PC12 cells, synaptotagmin, syntaxin 1A, neurotransmitter release, cell proliferation, synaptic gene expression, psychostimulants, dose-dependent effects
- MeSH terms
- Central Nervous System Stimulants, Animals, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Gene Expression Regulation, Membrane Glycoproteins, Methylphenidate, Nerve Tissue Proteins, Down-Regulation, PC12 Cells, Neurotransmitter Agents, Cell Proliferation, Syntaxin 1, Synaptotagmins, Synaptotagmin I, Rats
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