In vitro neuronal and vascular responses to 5-HT in rats chronically exposed to MDMA

1 This study examined the effects of chronic exposure of rats to 3,4-methyl enedioxymethamphetamine (MDMA) on [H-3]5-hydroxytryptamine ([H-3]5-HT) re-u ptake into purified rat brain synaptosomes, 5-HT-induced isometric contract ion of aortic rings and [H-3]5-HT re-uptake into rat aorta. 2 Rats were administered MDMA (20 mg kg(-1) i.p.) twice daily over 4 days. One, 7, 14 or 21 days post treatment, whole brain synaptosomes and descendi ng thoracic aortic rings were prepared for investigation. 3 Chronic MDMA treatment significantly reduced the maximum rate (V-max) of specific high-affinity [H-3]5-HT re-uptake 1 day after treatment and for up to 21 days post-final administration of MDMA. Direct application of MDMA ( 100 muM) abolished synaptosomal re-uptake of [H-3]5-HT in vitro. 4 Chronic MDMA administration significantly reduced the maximum contraction (E-max) to 5-HT at 1 and 7 days after treatment, but not at 14 or 21 days. 5 Chronic MDMA administration had no effect on sodium-dependent [H-3]5-HT r e-uptake into aorta 1 day after treatment, nor did 100 muM MDMA have any di rect effect on [H-3]5-HT uptake into aortic rings in vitro. 6 These results show, for the first time, an altered responsiveness of vasc ular tissue to MDMA after chronic administration. In addition, they demonst rate a difference in the sensitivity of central and peripheral 5-HT uptake systems to chronic MDMA exposure, and suggest that the action of MDMA in th e cardiovascular system does not arise from a direct effect of MDMA on peri pheral 5-HT transport.