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.