Adolescent exposure to methylphenidate impairs serial pattern learning in the serial multiple choice (SMC) task in adult rats James D. Rowan a, ⁎, Madison K. McCarty a , Shannon M.A. Kundey b , Crystal D. Osburn a , Samantha M. Renaud c , Brian M. Kelley d , Amanda Willey Matoushek e , Stephen B. Fountain c a Department of Psychology, Wesleyan College, Macon, GA 31210-4462, USA b Department of Psychology, Hood College, Frederick, MD 21701, USA c Department of Psychological Sciences, Kent State University, Kent, OH 44242-0001, USA d Department of Psychology, Bridgewater College, Bridgewater, VA 22812, USA e Department of Social Science, Bluefield State College, Bluefield, WV 24701, USA abstract article info Article history: Received 30 November 2014 Received in revised form 25 June 2015 Accepted 24 July 2015 Available online 28 July 2015 Keywords: Methylphenidate Ritalin Adolescent Exposure Sequential Behavior Serial Pattern Learning Serial Multiple Choice Task Phrasing Chunking Rats The long-term effects of adolescent exposure to methylphenidate (MPD) on adult cognitive capacity are largely unknown. We utilized a serial multiple choice (SMC) task, which is a sequential learning paradigm for studying complex learning, to observe the effects of methylphenidate exposure during adolescence on later serial pattern acquisition during adulthood. Following 20.0 mg/kg/day MPD or saline exposure for 5 days/week for 5 weeks during adolescence, male rats were trained to produce a highly structured serial response pattern in an octagonal operant chamber for water reinforcement as adults. During a transfer phase, a violation to the previously-learned pattern structure was introduced as the last element of the sequential pattern. Results indicated that while rats in both groups were able to learn the training and transfer patterns, adolescent exposure to MPD impaired learning for some aspects of pattern learning in the training phase which are learned using discrimination learning or se- rial position learning. In contrast adolescent exposure to MPD had no effect on other aspects of pattern learning which have been shown to tap into rule learning mechanisms. Additionally, adolescent MPD exposure impaired learning for the violation element in the transfer phase. This indicates a deficit in multi-item learning previously shown to be responsible for violation element learning. Thus, these results clearly show that adolescent MPD pro- duced multiple cognitive impairments in male rats that persisted into adulthood long after MPD exposure ended. © 2015 Elsevier Inc. All rights reserved. 1. Introduction Methylphenidate (MPD) is a psychostimulant that is related to caf- feine, amphetamine, and cocaine (Urban and Gao, 2013). At the height of its use in the 1990s, more than 2 million children were prescribed MPD (Challman and Lipsky, 2000) and it continues to be the preferred pharmacotherapy for the treatment of attention-deficit–hyperactivity disorder (ADHD) (Gray et al., 2007; Teter et al., 2003; Urban and Gao, 2013). MPD has also been identified as a potential drug of abuse and its illicit use has been on the rise within the past decade (Teter et al., 2003). While acute and chronic low doses of MPD (as prescribed for licit use) have been shown to improve cognitive function in rodents (Arnsten and Dudley, 2005; Berridge et al., 2006; Mohamed et al., 2011) chronic high doses of MPD have been shown to create more deleterious effects on the brain which often persist into adulthood (Bolanos et al., 2003; Brandon et al., 2001; Carlezon et al., 2003; Gray et al., 2007; LeBlanc-Duchin and Taukulis, 2007; Mcdougall et al., 1999; Scherer et al., 2010). For example, adolescent rats chronically ex- posed to high doses of MPD demonstrate impaired emotional response, poor object memory, and increased cross-sensitivity to other stimulants in adulthood (Bolanos et al., 2003; Brandon et al., 2001; Carlezon et al., 2003; LeBlanc-Duchin and Taukulis, 2007). High doses of MPD in prena- tal, juvenile, and adult animals have also been shown to cause cognitive deficits such as impairments in spatial memory, delayed alternation performance, and working memory (Arnsten and Dudley, 2005; Levin et al., 2011; Scherer et al., 2010). These studies illustrate that the effects of prolonged exposure to MPD treatment on brain structure and function might vary according to the dose and pattern of drug administration, as well as the complexity of the task involved (e.g., Bethancourt et al., 2009). Given the wide- spread usage of MPD among humans during the developmentally sensi- tive periods of childhood and adolescence, understanding potential long-term effects on neuronal systems and resultant behaviors is desir- able (e.g., Grund et al., 2006). However, research on the long-lasting ef- fects of MPD during adolescence is limited, and little work has examined Neurotoxicology and Teratology 51 (2015) 21–26 ⁎ Corresponding author. E-mail addresses: jrowan@wesleyancollege.edu (J.D. Rowan), mkmccarty@wesleyancollege.edu (M.K. McCarty), kundey@hood.edu (S.M.A. Kundey), cdosburn@wesleyancollege.edu (C.D. Osburn), srenaud@kent.edu (S.M. Renaud), bkelleyphd@gmail.com (B.M. Kelley), awilley@bluefieldstate.edu (A.W. Matoushek), sfountai@kent.edu (S.B. Fountain). http://dx.doi.org/10.1016/j.ntt.2015.07.007 0892-0362/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Neurotoxicology and Teratology journal homepage: www.elsevier.com/locate/neutera