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Vol. 295, Issue 1, 51-57, October 2000

Comparison between Intraperitoneal and Oral Methylphenidate Administration: A Microdialysis and Locomotor Activity Study1

Madina R. Gerasimov, Maja Franceschi, Nora D. Volkow, Andrew Gifford, Samuel J. Gatley, Douglas Marsteller, Patricia E. Molina2 and Stephen L. Dewey

Chemistry (M.R.G., D.M., S.L.D.) and Medical (M.F., N.D.V., A.G., S.J.G., P.E.M.) Departments, Brookhaven National Laboratory, Upton, New York; and Psychiatry Department, New York University School of Medicine, New York, New York (S.L.D.)

The therapeutic and stimulant properties of methylphenidate (MP), a drug commonly prescribed for the treatment of attention deficit hyperactivity disorder, have been attributed to increases in synaptic dopamine (DA) concentrations resulting from the blockade of DA transporters. In addition to obvious difficulties inherent in any interspecies comparison, interpretation of preclinical studies done with MP is further complicated by different routes of administration in animals (i.v. and i.p.) compared with humans (oral). In the present study we compared the effects of i.p. and intragastric (oral) MP both on rat nucleus accumbens DA assessed by in vivo microdialysis and on locomotor activity measured in a photocell apparatus. We also compared regional brain uptake and plasma levels of [3H]MP after administration of 5 mg/kg via both routes. Intraperitoneal MP (5 and 10 mg/kg) was approximately twice as potent as intragastric MP in terms of increasing extracellular DA levels and in stimulating locomotion. This was consistent with the higher brain uptake of [3H]MP when given i.p. rather than intragastrically. The dose of 2 mg/kg produced significant increases in both measurements when administered i.p., but not intragastrically. This study shows that relatively low doses of MP (2 mg i.p. and 5 mg intragastric) significantly increase extracellular DA and locomotor activity and indicates that the differences in the neurochemical and behavioral effects of MP between the intragastric and the i.p. routes are due to central drug bioavailability.

1 This research was carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886), and by the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155) and the National Institute on Drug Abuse (5RO-DA06278 and DA09490).

2 Current address: Department of Physiology, Louisiana State University, New Orleans, LA 70112.

0022-3565/00/2951-0051$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by U.S. Government


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