Oral methylphenidate establishes a conditioned place preference in rats

• Published in: Neuroscience letters Vol. 487; no. 3; pp. 293 - 296
• Main Authors: Wooters, Thomas E., Walton, Matthew T., Bardo, Michael T.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.01.2011; Elsevier
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Brain - drug effects; Central Nervous System Stimulants - administration & dosage; Conditioned place preference; Conditioning, Operant - drug effects; Fundamental and applied biological sciences. Psychology; Male; Methylphenidate; Methylphenidate - administration & dosage; Motor Activity - drug effects; Oral administration; Rat; Rats; Rats, Sprague-Dawley; Vertebrates: nervous system and sense organs; Conditioned place preference; Rat; Methylphenidate; Oral administration; Vertebrata; Mammalia; Animal; Rodentia
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.10.040

▶ There are no preclinical data on the abuse liability of oral methylphenidate (MPH). ▶ This study compared doses of oral and i.p. MPH on conditioned place preference (CPP). ▶ Each route of MPH established CPP. ▶ Higher doses of oral MPH are needed to establish CPP. ▶ This model can be used to study factors needed for oral MPH CPP. Emerging data suggest that illicit methylphenidate abuse is a growing problem. Although abuse of the drug typically occurs by the intranasal route, oral (per os; p.o.) methylphenidate also has abuse potential. The present study compared the effects of p.o. and intraperitoneal (i.p.) methylphenidate in rats using the conditioned place preference (CPP) procedure. Young adult male Sprague–Dawley rats were trained to consume oyster crackers injected initially with saline. Next, rats were randomly assigned to receive p.o. or i.p. methylphenidate (3 or 10mg/kg) or saline immediately or 30min prior to 30min conditioning trials. Methylphenidate or saline were each paired 4 times with an end compartment; preference for the methylphenidate-paired compartment was then assessed on a drug-free session. When given immediately prior to conditioning, significant CPP was obtained with both 3 and 10mg/kg of i.p. methylphenidate, but only with 10mg/kg of p.o. methylphenidate. When given 30min prior to conditioning, there was no evidence of CPP for any dose of i.p. or p.o. methylphenidate. These findings are the first demonstration that p.o. methylphenidate has rewarding effects, although i.p. methylphenidate is obtained at a 3mg/kg dose which did not establish CPP with p.o. administration. The lack of CPP following 30min pretreatment also suggests that conditioning may require the CS to be associated with a US of ascending, rather than descending, brain levels of methylphenidate. These results are consistent with clinical evidence of the reduced abuse liability of p.o. methylphenidate relative to methylphenidate taken by other (e.g., intranasal) routes.