title: Treatment with a clinically-relevant dose of methylphenidate alters NMDA receptor composition and synaptic plasticity in the juvenile rat prefrontal cortex.
abstract: 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.
authors: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors: Kimberly R
authors: KR
authors: Urban
authors: Yan-Chun
authors: YC
authors: Li
authors: Wen-Jun
authors: WJ
authors: Gao
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D016194:Receptors, N-Methyl-D-Aspartate; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor