Adolescent Exposure to Methylphenidate Alters the Activity of Rat Midbrain Dopamine Neurons
Overview
Affiliations
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.
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PharmGKB summary: methylphenidate pathway, pharmacokinetics/pharmacodynamics.
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