Subchronic Methylphenidate Administration Has No Effect on Locomotion, Emotional Behavior, or Water Maze Learning in Prepubertal Mice Melanie P. McFadyen Richard E. Brown Department of Psychology Dalhousie University Halifax, NS B3H 4J1, Canada Normand Carrey Department of Outpatient Psychiatry IWK-Grace Hospital, Halifax, NS B3H 3A1, Canada Received 24 July 2000; Accepted 14 August 2001 ABSTRACT: Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been con- ducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.). ß 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 123–132, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10059 Keywords: methylphenidate hydrochloride; Ritalin; attention deficit hyperactivity disorder; mice; behavior INTRODUCTION The psychostimulant methylphenidate hydrochloride (MPH, Ritalin) is administered to children for the treatment of attention deficit hyperactivity disorder (ADHD) (Greenhill, 1995). MPH is being prescribed to increasing numbers of children in the United States and Canada, as well as for longer treatment durations, often extending from childhood into adolescence (Klein, 1995; Minde, 1998; Solanto, 1998; Spencer et al., 1996). Neural development extends beyond adolescence into adulthood, with neural growth and differentiation continuing until 20 to 25 years of age (Benes, 1998; Giedd, 1999; Hockfield & Lombroso, 1998; Shumeiko, 1998). While there is considerable Correspondence to: R. E. Brown. E-mail: rebrown@is.dal.ca Contract grant sponsor: NSERC of Canada Contract grant number: A7441 Contract grant sponsor: QEII Hospital Research Foundation Contract grant number: XG 01-032 ß 2002 Wiley Periodicals, Inc.