Original article| Volume 54, ISSUE 12, P1338-1344, December 15, 2003

Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons

  • Cindy L Brandon
    Department of Anatomy and Cell Biology (CLB), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois, USA
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  • Michela Marinelli
    Department of Cellular and Molecular Pharmacology (MM, FJW), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois, USA
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  • Francis J White
    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.
    Department of Cellular and Molecular Pharmacology (MM, FJW), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois, USA
    Search for articles by this author



      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.


      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.


      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.


      Adolescent exposure to methylphenidate induces neuronal changes associated with increased addiction liability in rats.


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