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.
Keywords
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Article info
Publication history
Accepted:
July 16,
2003
Received in revised form:
July 11,
2003
Received:
March 20,
2003
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
