Brain Research Bulletin 82 (2010) 208–217 Contents lists available at ScienceDirect Brain Research Bulletin journal homepage: www.elsevier.com/locate/brainresbull Research report Psychostimulants given in adolescence modulate their effects in adulthood using the open field and the wheel-running assays P.B. Yang c , A.C. Swann b , N. Dafny a,b,∗ a Department of Neurobiology and Anatomy, The University of Texas - Medical School at Houston, P.O. Box 20708, Houston, TX 77225, United States b Department of Psychiatry and Behavioral Sciences, The University of Texas - Medical School at Houston, P.O. Box 20708, Houston, TX 77225, United States c Department of Anatomy and Neurobiology, University of California - Irvine School of Medicine, Irvine, CA 92697, United States article info Article history: Received 4 February 2010 Received in revised form 23 March 2010 Accepted 24 March 2010 Available online 31 March 2010 Keywords: Open field Wheel running Methylphenidate Behavior abstract Acute and chronic methylphenidate (MPD) were given to adults treated with MPD only in adulthood (adult I) and to adults that had been treated repeatedly during adolescence and adulthood (adult II). Two locomotor activity assays, the open field and the running wheel, were used in a dose response experiment to assess whether methylphenidate (MPD) treatment during adolescence would affect responses to MPD in adulthood. Each experiment lasted 11 days as follows: saline control on experimental day 1 (ED 1), followed by a single daily dose of saline, 0.6, 2.5, or 10 mg/kg MPD for 6 days (ED 2 to ED 7), 3 washout days with no drug administration (ED 8 to ED 10), and saline or MPD challenge on ED 11 at a dose identical to that given on ED 2 to ED 7. Acute MPD elicited characteristic dose response increases in locomotion in both experimental assays of adult I and adult II groups. Adult I and adult II rats tested in the open field assay exhibited sensitization to 2.5 mg/kg MPD and tolerance to 10 mg/kg MPD, while in the wheel-running assay all the three MPD doses elicited sensitization in both adult I and adult II rats. MPD treatment in adolescence did not change the baseline activity when animal reached adulthood. However, the responses to MPD in adult II rat groups were significantly different from the adult I group. Similar observations were noted during washout days. At the low and moderate MPD treatment both experimental assay exhibited similar observations while following the high dose of MPD treatment, the open field assay indicated that tolerance to MPD was expressed, while the wheel-running assay indicated that behavioral sensitization was developed. The distinction between the two assays and adult I and II differences are discussed. © 2010 Published by Elsevier Inc. 1. Introduction Methylphenidate (MPD) is an effective treatment for attention deficit hyperactivity disorder (ADHD) in adolescents and adults. ADHD is a behavioral disorder with onset in childhood that often continues into adulthood. This disorder is expressed by inattention and inability to remain focused or to concentrate for long peri- ods, hyperactivity and impulsivity [2,3,22,31,34,35,52,59,75]. MPD is frequently used for long-term management of ADHD. Recently the diagnosis of ADHD in children has increased, and it is estimated that 5–18% of school-age children (depending on geographical loca- tion) have been treated with MPD [1,18,31,32,38,43]. MPD shares many similarities with other stimulants, such as amphetamine and cocaine, that are known to be abused and exhibit many adverse effects [19,28,39,61]. ADHD symptoms continue into adulthood for ∗ Corresponding author at: The University of Texas Health Science Center at Hous- ton, P.O. Box 20708, Houston, Texas 77225-0708, United States. Tel.: +1 713 500 5616; fax: +1 713 500 2515. E-mail address: nachum.dafny@uth.tmc.edu (N. Dafny). up to 60% of patients, and MPD is frequently used across childhood, adolescence, and adulthood [1,2,31,38,41]. Administration of MPD to children raises concerns regarding its effects on the developing brain [4,6,22,33]. During devel- opment, overproduction of synaptic connections and receptors occurs, followed by pruning or programmed elimination. For exam- ple between 5 and 15 years of age, synaptic density in the frontal cortex decreases by 40% in humans [33,53]. The time course and the nature of ADHD expression parallel the pattern of overpro- duction and regressive synaptic elimination [5]. Rats exposed to MPD during the period equivalent to human adolescence experi- enced behavioral changes that endured into adulthood, suggesting that MPD can have effects on the developing brain that last into adulthood [4,12,48]. It was also reported that adult rats repeatedly treated with MPD during adolescent years were significantly more vulnerable to psychoactive substances [10,11,13,17,27]. How- ever, other reports present data suggesting that younger animals treated chronically with psychostimulants rarely exhibit behav- ioral sensitization, a persistent behavioral and motivational effect of stimulants [8,15,16]. Human studies [60,61] have shown that the blockade of dopamine (DA) transporter (DAT) accounts for the 0361-9230/$ – see front matter © 2010 Published by Elsevier Inc. doi:10.1016/j.brainresbull.2010.03.007