Reduction of [3H]6-nitroquipazine-labelled 5-hydroxytryptamine uptake sites in rat brain by 3,4-methylenedioxymethamphetamine.
Kenji Hashimoto, Tsuyoshi Goromaru
Fundamental and Clinical Pharmacology 1990 DOI: 10.1111/j.1472-8206.1990.tb00043.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rat brain (cerebral cortex) |
| Interventions | MDMA 6-nitroquipazine |
| Dose | MDMA 10 mg/kg ip twice daily; 6-nitroquipazine 5 mg/kg |
| Duration | 3 days of injections; assessed 1 week after the last injection |
| Measures | [3H]6-nitroquipazine-labelled 5-HT uptake sites, 5-HT and 5-HIAA concentrations |
| Topics | MDMA |
| Key findings | Repeated MDMA administration reduced cortical serotonin and 5-HIAA levels and the density of [3H]6-nitroquipazine-labelled serotonin uptake sites in rats one week after the last injection. Co-administration of the serotonin uptake inhibitor 6-nitroquipazine significantly prevented these reductions, which the authors interpret as indicating that the serotonin uptake carrier plays an important role in MDMA neurotoxicity. |
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.
Comparable studies
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Citations in the library
Cited by 5
- MDMA in Psychiatry: From PTSD to emerging indications, safety, and future directions Psychedelics October 14, 2025
- Effects of benzylpiperazine derivatives on the acute effects of 3,4-methylenedioxymethamphetamine in rat brain. Neuroscience Letters April 1, 1993
- Drug effects on distribution of [3H]3,4-methylenedioxymethamphetamine in mice. European Journal of Pharmacology April 1, 1993
- Effects of benzylpiperazine derivatives on the neurotoxicity of 3,4-methylenedioxymethamphetamine in rat brain. Brain Research September 1, 1992
- Antagonism of 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rat brain by 1-piperonylpiperazine. European Journal of Pharmacology September 1, 1992
Cites 7
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- The Background and Chemistry of MDMA Journal of Psychoactive Drugs October 1, 1986
- 5-hydroxytryptamine uptake blockers attenuate the 5-hydroxytryptamine-releasing effect of 3,4-methylenedioxymethamphetamine and related agents. European Journal of Pharmacology February 20, 1990
- Direct central effects of acute methylenedioxymethamphetamine on serotonergic neurons. European Journal of Pharmacology October 26, 1988
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