Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats.
BACKGROUND
Methylphenidate (MPH) is prescribed for the treatment of attention and hyperactivity disorders. We showed previously that early developmental exposure to MPH in rats causes behavioral alterations during adulthood, including reduced cocaine reward in place conditioning studies. Here we examined if early MPH exposure alters the ability of cocaine to potentiate the rewarding effects of electrical stimulation of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS).


METHODS
Rats received MPH or saline during pre-adolescence (P20-35) and were implanted with MFB stimulating electrodes at adulthood (P60). Rats then were tested with cocaine in the ICSS paradigm.


RESULTS
Cocaine dose-dependently decreased ICSS thresholds in all rats, but the threshold-lowering effects of cocaine were smaller in rats exposed to MPH during pre-adolescence. There were no differences between groups in sensitivity to the rewarding effects of MFB stimulation itself.


CONCLUSIONS
Early developmental exposure to MPH reduces the reward-related effects of cocaine in the ICSS paradigm. These results are consistent with previous studies in which early exposure to MPH reduced the ability of cocaine to establish conditioned place preferences, as well as the rewarding effects of sucrose and sexual behavior. Reduced sensitivity to these various types of reward may reflect general dysfunctions of brain reward systems.
Mague
Stephen D
SD
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.
Andersen
Susan L
SL
Carlezon
William A
WA
D000367:Age Factors; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012653:Self Stimulation / Q000187:drug effects
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003042:Cocaine