Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats
Jerrold S. Meyer, Mark Grande, Kenneth M Johnson, Syed F. Ali
International Journal of Developmental Neuroscience June 5, 2004 DOI: 10.1016/j.ijdevneu.2004.04.007 (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 |
| Duration | Postnatal days 1-4 (treatment), assessed at postnatal day 25, postnatal day 60, and 9 months of age |
| Topics | MDMA Serotonin |
| Keywords | Forebrain Endocrinology Serotonin transporter Hippocampus Neurotoxicity Pharmacology |
| Citations | 50 |
| Key findings | Neonatal MDMA exposure stimulates apoptotic cell death in forebrain areas and leads to long-term reorganization of forebrain serotonergic innervation, independent of body temperature. |
Abstract
Abstract 3,4‐Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug‐induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice‐daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1–4. Other drug‐treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase‐3 at postnatal day 5. The hippocampus showed significant MDMA‐related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter‐immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate‐putamen and nucleus accumbens shell. MDMA treatment also produced a two‐fold increase in the number of cleaved caspase‐3‐immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long‐term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA‐using women may be at heightened risk for abnormal neural and behavioral development.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 25
- 3,4-methylenedioxymethamphetamine (MDMA): current perspectives Substance Abuse and Rehabilitation November 1, 2013
- Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy Neurotoxicology and Teratology March 5, 2012
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
and 20 more in the library
Cites 16
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- 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
and 11 more in the library