title: Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.
abstract: The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease.
authors.affiliation: Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan. Electronic address: darakhshan-haleem@yahoo.com.
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
authors.affiliation: Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Qurrat-ul-Aen
authors.initials: QU
authors.lastname: Inam
authors.affiliation: Department of Biomedical Engineering, Sir Syed University of Engineering and Technology, Karachi, Pakistan.
authors.forename: Muhammad Abdul
authors.initials: MA
authors.lastname: Haleem
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Attention deficit hyperactivity disorder; Cognition; Emotion; Methylphenidate; Morris water maze test; Open field activity; Ritalin