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Reduction of [ 3 H]6‐nitroquipazine‐labelled 5‐hydroxytryptamine uptake sites in rat brain by 3,4‐methylenedioxymethamphetamine
Author(s) -
Hashimoto K.,
Goromaru T.
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00043.x
Subject(s) - mdma , serotonin , chemistry , metabolite , pharmacology , neurotoxin , p chloroamphetamine , 5 hydroxyindoleacetic acid , 5 ht receptor , ecstasy , endocrinology , serotonergic , biochemistry , medicine , receptor , psychiatry
Summary— 3,4‐Methylenedioxymethamphetamine (MDMA; Ecstasy) is a known neurotoxin to 5‐hydroxytryptamine (5‐HT; serotonin) nerve terminals. It has recently been demonstrated that [ 3 H]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 [ 3 H]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 [ 3 H]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 [ 3 H]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.