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Biol Psychiatry. 2005 Jan 15;57(2):120-5.

Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats.

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  • 1Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.



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).


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.


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.


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.

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