ORIGINAL ARTICLESEffects of monoamine oxidase inhibitors on cocaine discrimination in ratsGatch, Michael B.; Taylor, Cynthia M.; Flores, Elva; Selvig, Meghan; Forster, Michael J.Author Information Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA Correspondence and requests for reprints to Michael B. Gatch, PhD, Department of Pharmacology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2699, USA E-mail: [email protected] Sponsorship: Supported by NIH contract N01DA-7-8076 through the Cocaine Treatment Discovery Program of the National Institute on Drug Abuse. Received 31 May 2005 Accepted as revised 6 January 2006 Behavioural Pharmacology: March 2006 - Volume 17 - Issue 2 - p 151-159 doi: 10.1097/01.fbp.0000197459.08892.b5 Buy Metrics Abstract This study tested the time course of the discriminative stimulus effects of inhibitors of monoamine oxidase alone or in combination with cocaine. Male Sprague–Dawley rats were trained to discriminate cocaine (10 mg/kg, intraperitoneal) from saline using a two-lever choice methodology. The nonselective monoamine oxidase inhibitors tranylcypromine (0.01–5 mg/kg) and phenelzine (1–25 mg/kg), the monoamine oxidase-A selective compound clorgyline (1–25 mg/kg), and the monoamine oxidase-B selective compounds pargyline (0.005–50 mg/kg) and selegiline (1–25 mg/kg) were tested for substitution 15 min or 24 h following administration, and in combination with 10 mg/kg of cocaine 24 and 48 h after administration. At 15 min, selegiline fully substituted for the discriminative stimulus effects of cocaine, whereas all other compounds partially substituted. At 24 h, substitution of cocaine was diminished for all compounds except phenelzine, which produced a greater amount of substitution at 24 h than at 15 min. When cocaine was administered 24 h after clorgyline, selegiline, pargyline, and phenelzine, cocaine-appropriate responding was attenuated at intermediate doses of these drugs, whereas the highest doses did not alter cocaine-lever responding. All compounds except selegiline substantially decreased response rate and produced various adverse effects. At 48 h, the effects of all compounds except phenelzine were markedly reduced. Selectivity for monoamine oxidase-A or monoamine oxidase-B did not predict the ability to substitute for or attenuate the subjective effects of cocaine. These findings suggest that monoamine oxidase inhibitors can modulate the discriminative stimulus effects of cocaine for at least 24 h, and may be useful for treatment of cocaine abuse. © 2006 Lippincott Williams & Wilkins, Inc.