title: Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats.
abstract: Methylphenidate (MPH) is widely used as a "nootropic" agent and in the treatment of disorders of attention, and has been shown to modulate synaptic plasticity in vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered daily to male rats from postnatal day 42 for 15 days. The animals were tested daily in a radial maze. Long-term potentiation (LTP), a marker of neural plasticity, was induced in vivo in the prefrontal cortex after 2-3h, 15-18 days or 5 months without treatment. The behavioral performance of the 1mg/kg group improved, while that of animals that had received 5mg/kg deteriorated. In the 1 and 5mg/kg groups LTP induced 2-3h after the last MPH treatment was twice as large as in the controls. Further, 15-18 days after the last MPH administration, in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls. However, 5 months later, LTP in the 1mg/kg group was similar to controls and in the 5mg/kg group LTP could not be induced at all. No significant changes of LTP were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of MPH that improve learning coincide approximately with those that augment LTP. Secondly, MPH-induced increases in LTP can last for several weeks, but these may disappear over longer periods or deteriorate at high doses.
authors.affiliation: Laboratorio de Biopsicología, Escuela de Psicología, FAHU, USACH, Chile; Escuela de Psicología, FACSO, Universidad Central de Chile, FAHU, USACH, Chile.
authors.forename: H
authors.initials: H
authors.lastname: Burgos
authors.affiliation: Laboratorio de Biopsicología, Escuela de Psicología, FAHU, USACH, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Cofré
authors.affiliation: Laboratorio de Neurobiología, Facultad de Química y Biología, FAHU, USACH, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Hernández
authors.affiliation: Laboratorio de Neurofarmacología y Comportamiento, Facultad de Ciencias Médicas, FAHU, USACH, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Sáez-Briones
authors.affiliation: Escuela de Psicología, FCJS, Universidad Autónoma de Chile, FAHU, USACH, Chile.
authors.forename: R
authors.initials: R
authors.lastname: Agurto
authors.affiliation: Escuela de Psicología, FCJS, Universidad Autónoma de Chile, FAHU, USACH, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Castillo
authors.affiliation: Laboratorio de Neurociencias, Facultad de Química y Biología, Universidad de Santiago de Chile, FAHU, USACH, Chile. Electronic address: bernardo.morales@usach.cl.
authors.forename: B
authors.initials: B
authors.lastname: Morales
authors.affiliation: Laboratorio de Biopsicología, Escuela de Psicología, FAHU, USACH, Chile. Electronic address: marc.zeise@usach.cl.
authors.forename: M L
authors.initials: ML
authors.lastname: Zeise
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008774:Methylphenidate / Q000494:pharmacology*; D008839:Microelectrodes; D018697:Nootropic Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D018697:Nootropic Agents; D008774:Methylphenidate
keywords: Long-term potentiation; Metaplasticity; Methylphenidate; Prefrontal cortex