Behavioural Brain Research 218 (2011) 206–217 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Age and genetic strain differences in response to chronic methylphenidate administration Pamela B. Yang c , Derly O. Cuellar III a , Alan C. Swann b , Nachum Dafny a,b,∗ a Department of Neurobiology and Anatomy, The University of Texas-Medical School at Houston, P.O. Box 20708, Houston, TX 77225, USA b Department of Psychiatry and Behavioral Sciences, The University of Texas-Medical School at Houston, P.O. Box 20708, Houston, TX 77225, USA c Department of Anatomy and Neurobiology, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA article info Article history: Received 14 September 2010 Received in revised form 11 November 2010 Accepted 16 November 2010 Keywords: Locomotor Behavior Ritalin Adolescent Adult Genetic Strain abstract Methylphenidate hydrochloride (MPD) is a psychostimulant used in the treatment of attention deficit hyperactive disorder (ADHD) in adolescents and adults alike. Adolescence involves a period of neural development that is highly susceptible to environmental and pharmacological influence. Exposure to a psychostimulant like MPD during this crucial time period may cause permanent changes in neuronal function and formation. Another factor that may influence changes in neuronal function and formation is genetic variability. It has been reported that genetic variability affects both the initial behavioral response to drugs in general and psychostimulants in particular, and subsequently whether tolerance or sensitiza- tion is induced. The objective of the present study is to investigate the dose-response effects of repeated MPD administration (0.6, 2.5, or 10.0 mg/kg, i.p.) using an open field assay to investigate if there are dif- ferences between adolescent and adult Wistar-Kyoto (WKY), Spontaneously Hyperactive rat (SHR), and Sprague-Dawley (SD) rats, respectively, and if the genetic variability between the strains influences the degree of change in locomotion. The acute and chronic administration of MPD resulted in unique differ- ences in the level of increasing intensity in locomotor activity in each rat strain, with adult rats for the most part having a more intense increase in locomotor activity when compared to their adolescent coun- terparts. In conclusion, significant response differences among rat strains and age to acute and chronic MPD administration were observed only following the 2.5 and 10.0 mg/kg i.p. doses and not following the lower MPD dose (0.6 mg//kg i.p.). In addition the variability in activity among the rat strain and age suggests that MPD may affect the same neuronal circuit differently in each strain and age. The unique differences among the individual locomotor indices suggest also that each locomotor index is regulated by different neuronal circuits, and each affected differently by MPD. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Attention deficit hyperactive disorder (ADHD), a behavioral dis- order, is one of the most commonly diagnosed psychiatric disorders affecting 3–5% of school-aged children in the United States, possibly 17% if subclinical cases are included. ADHD affects 3–5% of adults in the United States, suggesting the disorder persists into adulthood [1,2]. Methylphenidate hydrochloride (MPD), commonly known as Ritalin is one of the most prescribed treatments for ADHD in adoles- cents and adults alike [3–5]. Its efficacy and safety have been well documented in many studies [6], but there is still a lack of informa- ∗ Corresponding author at: Department of Neurobiology and Anatomy, The Uni- versity of Texas-Medical School at Houston, P.O. Box 20708, Houston, TX 77225, USA. Tel.: +1 713 500 5616; fax: +1 713 500 0621. E-mail address: Nachum.Dafny@uth.tmc.edu (N. Dafny). tion regarding the influence of MPD on the developing brain and its long-term effects on neuronal function. In humans, normal neurodevelopment consists of an overpro- duction of synaptic connections with a subsequent elimination of these synapses by competitive inhibition. Synaptic pruning, usually occurs between 5 and 15 years of age, when the synaptic density of the prefrontal cortex decreases by approximately 40% [7,8]. It is thought that this synaptic reorganization may be a predisposing factor for many behavioral/psychiatric disorders including ADHD [7,9,10]. The treatment of ADHD in children using MPD parallels the timeframe of synaptic pruning, during which environmental and pharmacological influences exert a strong influence on neuronal formation and function [10,11]. Furthermore, rats exposed to MPD at an age approximating human childhood experienced behavioral changes that endured into adulthood, which suggests that MPD has a long-term effect on normal neurodevelopment [10,12]. The response to psychostimulants has been reported to vary with age 0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.11.034