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

This study examined the effects of chronic exposure of rats to 3,4‐methylenedioxymethamphetamine (MDMA) on [ 3 H]5‐hydroxytryptamine ([ 3 H]5‐HT) re‐uptake into purified rat brain synaptosomes, 5‐HT‐induced isometric contraction of aortic rings and [ 3 H]5‐HT re‐uptake into rat aorta. 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 descending thoracic aortic rings were prepared for investigation. Chronic MDMA treatment significantly reduced the maximum rate (V max ) of specific high‐affinity [ 3 H]5‐HT re‐uptake 1 day after treatment and for up to 21 days post‐final administration of MDMA. Direct application of MDMA (100 μ M ) abolished synaptosomal re‐uptake of [ 3 H]5‐HT in vitro . 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. Chronic MDMA administration had no effect on sodium‐dependent [ 3 H]5‐HT re‐uptake into aorta 1 day after treatment, nor did 100 μ M MDMA have any direct effect on [ 3 H]5‐HT uptake into aortic rings in vitro . These results show, for the first time, an altered responsiveness of vascular tissue to MDMA after chronic administration. In addition, they demonstrate 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 the cardiovascular system does not arise from a direct effect of MDMA on peripheral 5‐HT transport.British Journal of Pharmacology (2001) 134 , 1455–1460; doi: 10.1038/sj.bjp.0704402