title: Reduction of [3H]6-nitroquipazine-labelled 5-hydroxytryptamine uptake sites in rat brain by 3,4-methylenedioxymethamphetamine.
abstract: 3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a known neurotoxin to 5-hydroxytryptamine (5-HT; serotonin) nerve terminals. It has recently been demonstrated that [3H]6-nitroquipazine is a new radioligand for studying the 5-HT transport system in brain. Therefore, we examined the effects of repeated systemic administration (10 mg/kg ip, twice daily for 3 d) of MDMA on [3H]6-nitroquipazine-labelled 5-HT uptake sites in rat brain. Marked reductions in the concentrations of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) were observed in the cerebral cortex 1 week after the last injection of MDMA. In addition, the density of [3H]6-nitroquipazine-labelled 5-HT uptake sites was significantly decreased by MDMA. Furthermore, the reduction of 5-HT and 5-HIAA content and the density of [3H]6-nitroquipazine-labelled 5-HT uptake sites by MDMA were significantly prevented by co-administration of 6-nitroquipazine (5 mg/kg), a very potent and selective 5-HT uptake inhibitor. The present results indicate that the 5-HT uptake carrier plays an important role in the neurotoxic action of MDMA.
authors.affiliation: Department of Radiopharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, University of Fukuyama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Goromaru
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011814:Quipazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium
chemical_list: D012702:Serotonin Antagonists; D014316:Tritium; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D011814:Quipazine; D006897:Hydroxyindoleacetic Acid; C031227:6-nitroquipazine; D018817:N-Methyl-3,4-methylenedioxyamphetamine