Cardiovascular and sympathetic responses and reflex changes elicited by MDMA

The recreational use of 3,4-methylenedioxymethamphetamine (MDMA) has increa sed as have the number of clinical reports linking MDMA use with cardiovasc ular toxicity. Nonetheless, the cardiovascular and sympathetic nerve respon ses elicited by MDMA have not been well characterized. The purpose of this study was to characterize the mean arterial pressure (MAP), heart rate (HR) , and renal sympathetic nerve responses elicited by the acute administratio n of MDMA and to determine whether neurotoxic doses of MDMA change cardiova scular and/or cardiovascular reflex function. In conscious rats, MDMA or d- amphetamine elicited similar dose-dependent increases in MAP. MDMA elicited significant bradycardia at doses above 1.0 mg/kg. Pretreatment with phento lamine significantly reduced the duration but not the magnitude of the pres ser response elicited by MDMA. In pentobarbital-anesthetized rats, MDMA (0. 1 mg/kg) increased renal sympathetic nerve activity (RSNA; 33 +/- 10%), whi le larger doses significantly decreased RSNA (-91 +/- 3%, max). Neurotoxic doses of MDMA (20 mg/kg, s.c., b.i.d. for 4 days) significantly enhanced th e bradycardic component of the Bezold-Jarisch reflex elicited by i.v. serot onin when tested either 2 days or 2 weeks after the last neurotoxic treatme nt. However, neurotoxic treatment did not significantly affect baroreceptor reflex function. These results indicate that the acute administration of M DMA and d-amphetamine produce similar cardiovascular and sympathetic respon ses. Neurotoxic doses of MDMA can also significantly alter cardiovascular r eflex function. These findings raise the possibility that MDMA may have the potential to produce cardiovascular and/or cardiac toxicity similar to tha t elicited by other amphetamine analogs. (C) 2000 Elsevier Science Inc. All rights reserved.