Serotonergic Neurotoxicity of MDMA (Ecstasy) in the Developing Rat Brain
Annals of the New York Academy of Sciences June 1, 2002 DOI: 10.1111/j.1749-6632.2002.tb04179.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Neonatal rats |
| Intervention | MDMA |
| Dose | 10 mg/kg sc |
| Duration | Twice-daily injections from postnatal day 1 to 4; assessments at postnatal day 25 and 60 |
| Topics | MDMA Serotonin |
| Keywords | Neurotoxicity Pharmacology |
| Citations | 25 |
| Key findings | MDMA causes serotonergic neurotoxicity in neonatal rats independent of hyperthermia, with early hippocampal damage and delayed neocortical effects. |
Abstract
A bstract : The abused drug 3,4‐methylenedioxymethamphetamine (MDMA) damages fine serotonergic fibers and nerve terminals in adult organisms; however, developing animals seem less susceptible to this effect. One proposed hypothesis is that neonates are less sensitive to MDMA neurotoxicity because they fail to show drug‐induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 hours after each of twice‐daily MDMA (10 mg/kg sc) or saline injections given over the period from postnatal day (PD) 1 to 4. Other drug‐treated and control litters were maintained at normothermic temperatures after injection. Differential core body temperatures were achieved by placing pups (without the dam) in humidified, thermostatically controlled incubators. Temperatures were monitored with a thermocouple probe at 30‐minute intervals. Pups subsequently remained undisturbed until sacrifice at PD 25 and PD 60 for assessment of serotonergic damage by measuring 5‐HT transporter (SERT) binding in the hippocampus and neocortex as well as 5‐HT and 5‐HIAA concentrations (PD 25 only). Neonatal MDMA exposure led to significant reductions in both SERT binding and 5‐HT levels in the hippocampus at PD 25, independent of body temperature during treatment. Hippocampal SERT binding increased between PD 25 and PD 60 in both the MDMA and saline groups, but the MDMA‐related deficit remained unchanged. Interestingly, the neocortex showed no effect of MDMA at PD 25, but SERT binding was significantly reduced at PD 60. Thus, MDMA can exert serotonergic neurotoxicity in developing animals in the absence of elevated body temperature. Hippocampal serotonergic innervation is damaged early, whereas neocortical effects emerge at a later time. Furthermore, the tendency for serotonergic recovery may be less after neonatal MDMA exposure than exposure of adult animals.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 11
- Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects Journal of Psychopharmacology March 1, 2006
- Exposure to 3,4‐methylenedioxymethamphetamine (MDMA) on postnatal days 11–20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning International Journal of Developmental Neuroscience August 1, 2004
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
- Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats International Journal of Developmental Neuroscience June 5, 2004
- (+/–)3,4-Methylenedioxymethamphetamine (MDMA) Dose-Dependently Impairs Spatial Learning in the Morris Water Maze after Exposure of Rats to Different Five-Day Intervals from Birth to Postnatal Day Twenty Developmental Neuroscience 2009
and 6 more in the library
Cites 7
- (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals Neuropsychobiology 2000
- 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
- Age-dependent sensitivity of rats to the long-term effects of the serotonergic neurotoxicant (+/-)-3,4-methylenedioxymethamphetamine (MDMA) correlates with the magnitude of the MDMA-induced thermal response. Journal of Pharmacology and Experimental Therapeutics October 1, 1995
- 3,4-Methylenedioxymethamphetamine (Ecstasy)-Induced Learning and Memory Impairments Depend on the Age of Exposure during Early Development Journal of Neuroscience May 1, 2001
- Characteristics of pregnant women who use ecstasy (3, 4-methylenedioxymethamphetamine). Neurotoxicology and Teratology 2001
and 2 more in the library