The spin trap reagent alpha-phenyl-N-tert-butyl nitrone prevents 'ecstasy'-induced neurodegeneration of 5-hydroxytryptamine neurones.
M I Colado, A R Green
European Journal of Pharmacology July 14, 1995 DOI: 10.1016/0014-2999(95)00298-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Dark Agouti rats |
| Intervention | MDMA |
| Dose | MDMA 10 mg/kg i.p.; PBN 150 mg/kg i.p. |
| Duration | Assessed 7 days after MDMA administration |
| Measures | [3H]paroxetine binding, 5-HT and 5-HIAA levels |
| Topics | MDMA |
| Key findings | A single 10 mg/kg dose of MDMA reduced cortical and hippocampal serotonin and 5-HIAA by 40% and cortical paroxetine binding by about 30% at seven days. The spin trap PBN (150 mg/kg) fully prevented the paroxetine-binding loss and attenuated the serotonin and 5-HIAA losses, suggesting, in the authors' view, that MDMA-induced serotonin neurodegeneration involves reactive free radical formation. |
Abstract
Administration of a single dose (10 mg/kg i.p.) of 3,4-methylenedioxy-methamphetamine (MDMA or 'ecstasy') produced a 40% loss of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cortex and hippocampus of Dark Agouti rats 7 days later. Binding of [3H]paroxetine to the presynaptic 5-HT nerve terminals in cortex was decreased by approximately 30%. Injection of the spin trap reagent alpha-phenyl-N-tert-butyl nitrone (PBN; 150 mg/kg i.p.) 10 min prior and 120 min post MDMA administration totally prevented the loss in [3H]paroxetine binding in the cortex and attenuated the loss of 5-HT and 5-HIAA in both brain regions. PBN alone had no effect on [3H]paroxetine binding or brain 5-HT content. These data suggest that MDMA produces neurodegeneration of 5-HT neurones because of reactive free radical formation.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 34
- A study of the neurotoxic effect of MDMA (‘ecstasy’) on 5‐HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy British Journal of Pharmacology June 1, 1997
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype British Journal of Pharmacology August 1, 1995
- A study of the mechanisms involved in the neurotoxic action of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain British Journal of Pharmacology December 1, 2001
- The mechanisms involved in the long‐lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)‐induced degeneration of 5‐HT nerve endings in rat brain British Journal of Pharmacology September 1, 2001
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Cites 7
- The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype British Journal of Pharmacology August 1, 1995
- 5‐HT loss in rat brain following 3, 4‐methylenedioxymethamphetamine (MDMA), p‐chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine British Journal of Pharmacology March 1, 1993
- A study of the mechanism of MDMA (‘Ecstasy’)‐induced neurotoxicity of 5‐HT neurones using chlormethiazole, dizocilpine and other protective compounds British Journal of Pharmacology 1994
- Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). Psychopharmacology June 1995
- Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA ('Ecstasy') to rats. Neuropharmacology December 1994
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