PT - JOURNAL ARTICLE AU - Beth Levant AU - Troy J. Zarcone AU - Paul F. Davis AU - Marlies K. Ozias AU - Stephen C. Fowler TI - Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task AID - 10.1124/jpet.110.174425 DP - 2011 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 83--91 VI - 337 IP - 1 4099 - http://jpet.aspetjournals.org/content/337/1/83.short 4100 - http://jpet.aspetjournals.org/content/337/1/83.full SO - J Pharmacol Exp Ther2011 Apr 01; 337 AB - Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an “alcove”) in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D1-like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry.