Microglial and astroglial activation by 3,4‐methylenedioxymethamphetamine (MDMA) in mice depends on S(+) enantiomer and is associated with an increase in body temperature and motility
Lucia Frau, Nicola Simola, Antonio Plumitallo, Micaela Morelli
Journal of Neurochemistry October 20, 2012 DOI: 10.1111/jnc.12060 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | racemic MDMA |
| Dose | 4 × 10 mg/kg for enantiomers, 4 × 20 mg/kg for racemic MDMA |
| Topics | MDMA |
| Keywords | Striatum Pharmacology Nucleus accumbens Midbrain Microglia Substantia nigra Dopamine |
| Citations | 46 |
| Key findings | S(+)-MDMA, but not R(−)-MDMA, activates microglia and astroglia in the mouse striatum, and combining the enantiomers produces no synergistic effect beyond additivity. |
Abstract
Abstract Evidence is accumulating to suggest that 3,4‐methylenedioxymethamphetamine ( MDMA ) has neurotoxic and neuroinflammatory properties. MDMA is composed of two enantiomers with different biological activities. In this study, we evaluated the in vivo effects of S(+)‐ MDMA , R(−)‐ MDMA , and S(+)‐ MDMA in combination with R(−)‐ MDMA on microglial and astroglial activation compared with racemic MDMA , by assessment of complement type 3 receptor ( CD 11b) and glial fibrillary acidic protein ( GFAP ) immunoreactivity in the mouse striatum, nucleus accumbens, motor cortex, and substantia nigra. Motor activity and body temperature were also measured, to elucidate the physiological modifications paired with the observed glial changes. Similar to racemic MDMA (4 × 20 mg/kg), S(+)‐ MDMA (4 × 10 mg/kg) increased both CD 11b and GFAP in the striatum, although to a lower degree, whereas R(−)‐ MDMA (4 × 10 mg/kg) did not induce any significant glial activation. Combined administration of S(+) plus R(−)‐ MDMA did not induce any further activation compared with S(+)‐ MDMA . In all other areas, only racemic MDMA was able to slightly activate the microglia, but not the astroglia, whereas enantiomers had no effect, either alone or in combination. Racemic MDMA and S(+)‐ MDMA similarly increased motor activity and raised body temperature, whereas R(−)‐ MDMA affected neither body temperature nor motor activity. Interestingly, the increase in body temperature was correlated with glial activation. The results show that no synergism, but only additivity of effects, is caused by the combined administration of S(+)‐ and R(−)‐ MDMA , and underline the importance of investigating the biochemical and behavioral properties of the two MDMA enantiomers to understand their relative contribution to the neuroinflammatory and neurotoxic effects of MDMA .
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice Movement Disorders September 20, 2013
- Separating the agony from ecstasy: R(−)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice Neuropharmacology October 6, 2017
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
and 20 more in the library
Cites 18
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- Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice Journal of Neurochemistry September 24, 2008
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- MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research Neuropsychobiology 2009
- Early loss of dopaminergic terminals in striosomes after MDMA administration to mice Synapse October 25, 2007
and 13 more in the library