Abstract
Rationale
Previous studies in rodents show that early exposure to methylphenidate alters later responsiveness to drugs of abuse. An interesting feature of these studies is that early methylphenidate treatment decreases the rewarding value of cocaine when measured by conditioned place preference (CPP), but the same treatment increases cocaine self-administration.
Objective
The goal of the present study was to examine the effects of early methylphenidate exposure on cocaine-induced responding using both reward paradigms.
Methods
Rats were treated with methylphenidate (0, 2, or 5 mg/kg) from postnatal days (PDs) 11 to 20, and then cocaine-induced CPP or cocaine self-administration was measured in separate groups of rats in adulthood. The CPP procedure included 8 days of acquisition training, 8 days of extinction training, and a reinstatement test. Rats were conditioned with 0, 10, or 20 mg/kg cocaine. Reinstatement was assessed after a priming dose of cocaine (10 mg/kg). For the self-administration experiment, a jugular catheter was implanted and rats were trained to press a lever reinforced with cocaine (0.25 or 0.75 mg/kg/infusion) on a fixed ratio (FR) one schedule. Rats were gradually moved from an FR1 to an FR10 schedule and, after criterion was reached, rats were placed on a progressive ratio schedule for 5 days.
Results
Cocaine produced robust rewarding effects as determined by both the CPP and self-administration experiments; however, early methylphenidate exposure only enhanced the reinforcing effects of cocaine on the self-administration paradigm. Interestingly, this methylphenidate enhancement was only seen in male rats.
Conclusions
These data suggest that in males, methylphenidate enhances the reinforcing value of cocaine, but not cocaine-associated cues.
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Acknowledgments
We gratefully acknowledge Dr. Janet Neisewander for her substantial assistance with the self-administration procedure. We also thank Dr. Sanders McDougall for his meticulous editing of the manuscript. This work was supported by PHS grant GM073842.
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Crawford, C.A., Baella, S.A., Farley, C.M. et al. Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats. Psychopharmacology 213, 43–52 (2011). https://doi.org/10.1007/s00213-010-2011-8
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DOI: https://doi.org/10.1007/s00213-010-2011-8