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
María Isabel Colado, Esther O’shea, R Granados, Aditya Misra, Tracey K. Murray, A. R. Green
British Journal of Pharmacology June 1, 1997 DOI: 10.1038/sj.bjp.0701201 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Pregnant rats and their neonates |
| Intervention | MDMA |
| Dose | 20 mg/kg twice daily on days 14–17 of gestation; 40 mg/kg single dose for adult and neonatal lipid peroxidation experiments |
| Duration | Days 14–17 of gestation for prenatal exposure; 3 and 6 hours post-injection for lipid peroxidation; 1 week after parturition for maternal brain analysis |
| Topics | MDMA Serotonin |
| Keywords | Endocrinology Striatum Teratology Tbars Pregnancy Gestation Hippocampus Hallucinogen Cerebrum Pharmacology Anesthesia Dopamine |
| Citations | 176 |
| Key findings | MDMA administered to pregnant rats during late gestation damaged serotonin nerve terminals in the mothers' brains but not in the brains of their newborn pups. |
Abstract
It is well established that 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) is neurotoxic and produces long term degeneration of cerebral 5‐hydroxytryptamine (5‐HT) nerve terminals in many species. Since MDMA is used extensively as a recreational drug by young people, it is being ingested by many women of child bearing age. We have therefore examined the effect of administering high doses of MDMA to rats during pregnancy on the cerebral content of both the dams and the neonates. MDMA (20 mg kg −1 , s.c.) was injected twice daily on days 14–17 of the gestation period. The initial dose produced a marked hyperthermic response in the dam which was progressively attenuated in both peak height and area under the curve following further doses of the drug. The body weight of the dams decreased during the period of treatment. There was a modest decrease in litter size (−20%) of the MDMA‐treated dams. The concentration of 5‐HT and its metabolite 5‐HIAA was decreased by over 65% in the hippocampus and striatum and 40% in the cortex of the dams 1 week after parturition. In contrast, the content of 5‐HT and 5‐HIAA in the dorsal telencephalon of the pups of the MDMA‐treated dams was the same as that seen in tissue from pups born to control animals. Administration of MDMA (40 mg kg −1 , s.c.) to adult rats increased thiobarbituric acid reacting substances (TBARS) in cortical tissue 3 h and 6 h later, indicating increased lipid peroxidation. No increase in TBARS was seen in the cortical tissue of 7–10 day neonates injected with this dose of MDMA 3 h or 6 h earlier. The data suggest that exposure to MDMA in utero during the maturation phase does not produce damage to 5‐HT nerve terminals in the foetal rat brain, in contrast to the damage seen in the brains of the mothers. This may be due to MDMA being metabolized to free radical producing entities in the adult brain but not in the immature brain or, alternatively, to more effective or more active free radical scavenging mechanisms being present in the immature brain. British Journal of Pharmacology (1997) 121 , 827–833; doi: 10.1038/sj.bjp.0701201
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 42
- 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 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
- Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT Synapse 2001
- Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration British Journal of Pharmacology February 1, 1999
- Role of hyperthermia in the protective action of clomethiazole against MDMA (‘ecstasy’)‐induced neurodegeneration, comparison with the novel NMDA channel blocker AR‐R15896AR British Journal of Pharmacology June 1, 1998
and 37 more in the library
Cites 15
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- 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
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- 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
and 10 more in the library