Ultrastructural characterization of tryptophan hydroxylase 2-specific cortical serotonergic fibers and dorsal raphe neuronal cell bodies after MDMA treatment in rat.
Csaba Ádori, Péter Low, Rómeó D. Andó, Lise Gutknecht, Dorottya Pap, Ferencné Truszka, József Takács, Gábor G. Kovács, Klaus‐peter Lesch, György Bagdy
Psychopharmacology February 2011 DOI: 10.1007/s00213-010-2041-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Cross-sectional Peer reviewed |
|---|---|
| Population | Adolescent Dark Agouti rats |
| Intervention | MDMA |
| Dose | 15 mg/kg i.p. |
| Duration | 3 days after treatment |
| Topics | MDMA Serotonin |
| Key findings | MDMA treatment caused destruction of microtubules in cortical serotonergic axons, with some axons showing degenerating mitochondria or membrane whorls, but no ultrastructural changes in dorsal raphe cell bodies or proximal neurites, indicating selective axonal damage. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to cause selective long-term serotonergic damage. The aim of this study was to characterize the ultrastructure of serotonergic pericarya and proximal neurites in the dorsal raphe nucleus as well as the ultrastructure of serotonergic axons in the frontal cortex of adolescent Dark Agouti rats 3 days after treatment with 15 mg/kg i.p. MDMA. Light microscopic immunohistochemistry and pre-embedding immunoelectron microscopy with a novel tryptophan hydroxylase-2 (Tph2) specific antibody, as a marker of serotonergic structures. Light microscopic analysis showed reduced serotonergic axon density and aberrant swollen varicosities in the frontal cortex of MDMA-treated animals. According to the electron microscopic analysis, Tph2 exhibited diffuse cytoplasmic immunolocalization in dorsal raphe neuronal cell bodies. The ultrastructural-morphometric analysis of these cell bodies did not indicate pathological changes or significant alteration in the cross-sectional areal density of any examined organelles. Proximal serotonergic neurites in the dorsal raphe exhibited no ultrastructural alteration. However, in the frontal cortex among intact fibers, numerous serotonergic axons with destructed microtubules were found. Most of their mitochondria were intact, albeit some injured axons also contained degenerating mitochondria; moreover, a few of them comprised confluent membrane whorls only. Our treatment protocol does not lead to ultrastructural alteration in the serotonergic dorsal raphe cell bodies and in their proximal neurites but causes impairment in cortical serotonergic axons. In these, the main ultrastructural alteration is the destruction of microtubules although a smaller portion of these axons probably undergo an irreversible damage.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study. PLoS One June 10, 2016
- Methylenedioxymethamphetamine (MDMA, 'Ecstasy'): Neurodegeneration versus Neuromodulation Pharmaceuticals July 5, 2011
- The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research Behavioural Brain Research February 10, 2026
- Differential role of dose and environment in initiating and intensifying neurotoxicity caused by MDMA in rats BMC Pharmacology and Toxicology August 5, 2019
- Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3 weeks after MDMA administration in Dark Agouti rats. BMC Genomics August 2, 2018
and 1 more in the library
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and 10 more in the library