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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.
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