Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task□S

Methylphenidate is a psychostimulant widely used in the treat-ment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylpheni-date (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 para-digm 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 methylpheni-date increased locomotion in a dose-related manner. The in-troduction 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 signifi-cantly 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 differ-ences in pharmacokinetics and dopaminergic neurochemistry