title: Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents.
abstract: Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3mg/kg) improving inhibition, and high dose (3mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity.
authors.affiliation: University of Pittsburgh, Department of Neuroscience, A210 Langley Hall, Pittsburgh, PA 15260, United States.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Simon
authors.affiliation: University of Pittsburgh, Department of Neuroscience, A210 Langley Hall, Pittsburgh, PA 15260, United States. Electronic address: bita@pitt.edu.
authors.forename: Bita
authors.initials: B
authors.lastname: Moghaddam
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000523:psychology*; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004305:Dose-Response Relationship, Drug; D007266:Inhibition, Psychological; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017711:Nonlinear Dynamics; D011581:Psychological Tests; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Development; Dopamine; Impulsivity; Instrumental behavior; Inverted U; Reward; Ritalin