Vol. 302, Issue 3, 898-907, September 2002

Changes in Cardiovascular Responsiveness and Cardiotoxicity Elicited during Binge Administration of Ecstasy

Lisa A. Badon, Alissa Hicks, Kevin Lord, Brian A. Ogden, Suzanne Meleg-Smith and Kurt J. Varner

Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center (A.H., K.L., B.A.O., K.J.V.); Loyola University New Orleans (L.A.B.); and Department of Pathology, Tulane School of Medicine, New Orleans, Louisiana (S.M.-S.)

The recreational use of 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is often characterized by a repeated pattern of frequent drug administrations (binge) followed by a period of abstinence. Radiotelemetry was used to characterize the cardiovascular responses elicited during three MDMA binges (3 or 9 mg/kg b.i.d. for 4 days), each of which was separated by a 10-day MDMA-free period. The heart rate and mean arterial pressure (MAP) responses elicited by 3-mg/kg doses of MDMA were consistent within and between the three binges. In the first binge the 9-mg/kg doses of MDMA increased MAP and produced a biphasic (decrease/increase) heart rate response. The bradycardia elicited by MDMA in the first binge (75 bpm) was enhanced in the second and third binges (186 and 287 bpm, respectively). Significant hypotension accompanied the increased bradycardic responses. Atropine abolished the hypotension and significantly attenuated the bradycardic responses. The MAP and heart rate responses elicited by sodium nitroprusside, acetylcholine, phenylephrine, and serotonin (5-HT) were evaluated before each binge and 10 days after the last binge. The hypotension, but not the tachycardia elicited by sodium nitroprusside was attenuated by the repeated administration of MDMA. The responses to phenylephrine, acetylcholine, and 5-HT were unaltered after MDMA. The hearts of treated rats contained foci of inflammatory infiltrates (lymphocytes and macrophages), some of which contained necrotic cells and/or disrupted cytoarchitecture. MDMA produced cardiac arrhythmias in some rats. These results indicate that the binge administration of MDMA can significantly alter cardiovascular and cardiovascular reflex function and produce cardiac toxicity.