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Treatment with a clinically-relevant dose of methylphenidate alters NMDA receptor composition and synaptic plasticity in the juvenile rat prefrontal cortex
Journal article   Open access   Peer reviewed

Treatment with a clinically-relevant dose of methylphenidate alters NMDA receptor composition and synaptic plasticity in the juvenile rat prefrontal cortex

Kimberly R Urban, Yan-Chun Li and Wen-Jun Gao
Neurobiology of learning and memory, v 101, pp 65-74
Mar 2013
DOI: https://doi.org/10.1016/j.nlm.2013.01.004
PMID: 23333502
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.nlm.2013.01.004View
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Abstract

Receptors, N-Methyl-D-Aspartate - drug effects Central Nervous System Stimulants - pharmacology Receptors, N-Methyl-D-Aspartate - metabolism Neuronal Plasticity - drug effects Rats Male Methylphenidate - pharmacology Long-Term Synaptic Depression - drug effects Excitatory Postsynaptic Potentials - drug effects Rats, Sprague-Dawley Patch-Clamp Techniques Animals Prefrontal Cortex - drug effects Long-Term Potentiation - drug effects Prefrontal Cortex - metabolism Female Synaptic Transmission - drug effects
Methylphenidate (Ritalin, MPH) is the most commonly prescribed psychoactive drug for children. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, its cellular mechanisms of action and potential long-term effects are poorly understood. We recently reported that a clinically relevant (1 mg/kg i.p., single injection) dose of MPH significantly decreased neuronal excitability in the juvenile rat prefrontal cortical neurons. Here we further explore the actions of acute treatment with MPH on the level of NMDA receptor subunits and NMDA receptor-mediated short- and long-term synaptic plasticity in the juvenile rat prefrontal cortical neurons. We found that a single dose of MPH treatment (1 mg/kg, intraperitoneal) significantly decreased the surface and total protein levels of NMDA receptor subunits NR1 and NR2B, but not NR2A, in the juvenile prefrontal cortex. In addition, the amplitude, decay time and charge transfer of NMDA receptor-mediated EPSCs were significantly decreased whereas the amplitude and short-term depression of AMPA receptor-mediated EPSCs were significantly increased in the prefrontal neurons. Furthermore, MPH treatment also significantly increased the probability and magnitude of LTP induction, but had only a small effect on LTD induction in juvenile rat prefrontal cortical neurons. Our data thus present a novel mechanism of action of MPH, i.e., changes in glutamatergic receptor-mediated synaptic plasticity following early-life treatment. Furthermore, since a single dosage resulted in significant changes in NMDA receptors, off-label usage by healthy individuals, especially children and adolescents, may result in altered potential for plastic learning.

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Web of Science research areas
Behavioral Sciences
Neurosciences
Psychology
Psychology, Multidisciplinary
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