Enduring behavioral effects of early exposure to methylphenidate in rats.
BACKGROUND
Methylphenidate (MPH) is a stimulant prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulant drugs can cause enduring behavioral adaptations, including altered drug sensitivity, in laboratory animals. We examined how early developmental exposure to stimulants affects behavior in several rodent models.


METHODS
Rats received MPH or cocaine during preadolescence (P20-35). Behavioral studies began during adulthood (P60). We compared how early exposure to MPH and cocaine affects sensitivity to the rewarding and aversive properties of cocaine using place conditioning. We also examined the effects of early exposure to MPH on depressive-like signs using the forced swim test, and habituation of spontaneous locomotion, within activity chambers.


RESULTS
In place-conditioning tests, early exposure to MPH or cocaine each made moderate doses of cocaine aversive and high doses less rewarding. Early MPH exposure also caused depressive-like effects in the forced swim test, and it attenuated habituation to the activity chambers.


CONCLUSIONS
Early exposure to MPH causes behavioral changes in rats that endure into adulthood. Some changes (reduced sensitivity to cocaine reward) may be beneficial, whereas others (increases in depressive-like signs, reduced habituation) may be detrimental. The effects of MPH on cocaine-related behaviors may be a general consequence of early stimulant exposure.
Carlezon
William A
WA
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.
Mague
Stephen D
SD
Andersen
Susan L
SL
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007103:Immobilization; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D003042:Cocaine