Progression and Persistence of Neurotoxicity Induced by MDMA in Dopaminergic Regions of the Mouse Brain and Association with Noradrenergic, GABAergic, and Serotonergic Damage.
Giulia Costa, Micaela Morelli, Nicola Simola
Neurotoxicity Research November 2017 DOI: 10.1007/s12640-017-9761-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort (animal study) Peer reviewed |
|---|---|
| Population | Mice treated with MDMA and evaluated by immunohistochemistry at postnatal days 85, 110, 138, or 214 |
| Intervention | MDMA |
| Dose | 10 mg/kg twice a week |
| Duration | 14, 28, or 36 administrations; follow-up up to 3 months after MDMA discontinuation |
| Measures | tyrosine hydroxylase (TH), dopamine transporter (DAT), noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), serotonin transporter (SERT) |
| Topics | MDMA Serotonin |
| Keywords | Amphetamine-related drugs Dopamine transporter Glutamic acid decarboxylase-67 Noradrenaline transporter Serotonin transporter Tyrosine hydroxylase |
| Key findings | Mice given 28 or 36 MDMA administrations (10 mg/kg twice weekly) showed reduced dopamine transporter-positive fibers in caudate-putamen and medial prefrontal cortex and reduced tyrosine hydroxylase-positive nigral neurons, with similar effects at 36 doses plus reduced striatal, cortical, and hippocampal tyrosine hydroxylase fibers. Dopaminergic and GAD-67 reductions persisted three months after discontinuation, while serotonin transporter levels were unchanged. The authors propose the dopaminergic damage may associate with GABAergic but not noradrenergic or serotonergic damage. |
Abstract
The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to characterize how the number of administrations influenced the severity of MDMA-induced dopaminergic damage and to describe the localization and persistence of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we investigated whether dopaminergic damage was associated with noradrenergic, GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin transporter (SERT). Mice received 14, 28, or 36 MDMA administrations (10 mg/kg twice a week) and were sacrificed at different time points (postnatal days 85, 110, 138, or 214) for immunohistochemical evaluation. Mice receiving 28 administrations showed reduced levels of DAT-positive fibers in caudate-putamen (CPu) and medial prefrontal cortex (mPFC) and reduced levels of TH-positive nigral neurons. These mice also displayed increased NET-positive hippocampal fibers, reduced GAD-67-positive neurons in CPu and hippocampus, and reduced GAD-67-positive fibers in mPFC. Similar effects of MDMA on DAT, TH, and GAD-67 were found in mice receiving 36 administrations, which also displayed reduced levels of striatal, cortical, and hippocampal TH-immunoreactive fibers. The reductions in dopaminergic markers and GAD-67 persisted at 3 months after MDMA discontinuation. Finally, MDMA never modified the levels of SERT. These results provide further insight into the localization and persistence of MDMA-induced dopaminergic damage and show that this effect may associate with GABAergic but not noradrenergic or serotonergic damage.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 14
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings Neural Regeneration Research February 22, 2024
- Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2023
and 9 more in the library
Cites 30
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Patterns of simultaneous polysubstance use in drug using university students Human Psychopharmacology: Clinical and Experimental June 1, 2006
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
and 25 more in the library