PMID- 11724751 OWN - NLM STAT- MEDLINE DCOM- 20020114 LR - 20181113 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 134 IP - 7 DP - 2001 Dec TI - In vitro neuronal and vascular responses to 5-HT in rats chronically exposed to MDMA. PG - 1455-60 AB - 1. 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. 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 descending thoracic aortic rings were prepared for investigation. 3. 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 microM) abolished synaptosomal re-uptake of [(3)H]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 [(3)H]5-HT re-uptake into aorta 1 day after treatment, nor did 100 microM MDMA have any direct effect on [(3)H]5-HT uptake into aortic rings in vitro. 6. 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. FAU - Cannon, D M AU - Cannon DM AD - Department of Pharmacology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. FAU - Keenan, A K AU - Keenan AK FAU - Guiry, P J AU - Guiry PJ FAU - Buon, C AU - Buon C FAU - Baird, A W AU - Baird AW FAU - McBean, G J AU - McBean GJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 10028-17-8 (Tritium) RN - 333DO1RDJY (Serotonin) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Aorta, Thoracic/*drug effects/metabolism/physiology MH - Biological Transport/drug effects MH - Dose-Response Relationship, Drug MH - In Vitro Techniques MH - Male MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Rats MH - Rats, Wistar MH - Serotonin/*pharmacokinetics/pharmacology MH - Synaptosomes/*drug effects/metabolism MH - Tritium MH - Vasoconstriction/drug effects PMC - PMC1573088 EDAT- 2001/11/29 10:00 MHDA- 2002/01/15 10:01 PMCR- 2002/12/01 CRDT- 2001/11/29 10:00 PHST- 2001/11/29 10:00 [pubmed] PHST- 2002/01/15 10:01 [medline] PHST- 2001/11/29 10:00 [entrez] PHST- 2002/12/01 00:00 [pmc-release] AID - 0704402 [pii] AID - 10.1038/sj.bjp.0704402 [doi] PST - ppublish SO - Br J Pharmacol. 2001 Dec;134(7):1455-60. doi: 10.1038/sj.bjp.0704402.