Reduction of [3H]6‐nitroquipazine‐labelled 5‐hydroxytryptamine uptake sites in rat brain by 3,4‐methylenedioxymethamphetamine

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Abstract
Summary—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.