Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons
Received 20 March 2003; received in revised form 11 July 2003; accepted 16 July 2003.
Abstract
Background
Methylphenidate is commonly used to treat children and adolescents with attention-deficit/hyperactivity disorder. A health concern is its long-term effects with respect to later stimulant exposure. We reported that repeated exposure to a low dose of methylphenidate during adolescence increases self-administration of a low, typically nonreinforcing dose of cocaine in adult rats. We also showed that enhanced vulnerability to cocaine is associated with elevated impulse and bursting activity of midbrain dopamine neurons in drug-naïve adult rats and might constitute a substrate critically associated with abuse liability. Thus we sought to determine whether repeated exposure to low-dose methylphenidate in adolescence alters dopamine neuronal excitability in adulthood.
Methods
After 3-day and 2-week withdrawal from repeated low-dose adolescent exposure to methylphenidate, we used extracellular single-unit recording in chloral hydrate–anesthetized rats to determine basal firing and bursting activity of midbrain dopamine neurons and dopamine autoreceptor sensitivity to the D2-class direct receptor agonist quinpirole.
Results
Dopamine neuronal impulse activity was increased after 3 days and decreased after 2 weeks' withdrawal from methylphenidate given in adolescence. No difference between groups was evident with respect to autoreceptor sensitivity to quinpirole.
Conclusions
Adolescent exposure to methylphenidate induces neuronal changes associated with increased addiction liability in rats.
aDepartment of Anatomy and Cell Biology (CLB), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois, USA
bDepartment of Cellular and Molecular Pharmacology (MM, FJW), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois, USA
Address reprint requests to Dr. Francis J. White, Finch University of Health Sciences, Chicago Medical School, Department of Cellular and Molecular Pharmacology, 3333 Green Bay Road, North Chicago IL 60048, USA.
ABSTRACT