Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons.
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.
Brandon
Cindy L
CL
Department of Anatomy and Cell Biology (CLB), Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60048, USA.
Marinelli
Michela
M
White
Francis J
FJ
D000200:Action Potentials / Q000187:drug effects; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D008774:Methylphenidate / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013995:Time; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D012457:Salicylamides; D008774:Methylphenidate; D019257:Quinpirole; C045989:eticlopride; D004298:Dopamine