Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat
Csaba Ádori, Rómeó D. Andó, Mária Szekeres, Lise Gutknecht, Gábor G. Kovács, László Hunyady, Klaus‐peter Lesch, György Bagdy
The Journal of Comparative Neurology March 31, 2011 DOI: 10.1002/cne.22631 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Adolescent/young adult male Dark Agouti rats |
| Intervention | MDMA |
| Dose | 15 mg/kg i.p. |
| Duration | 4 weeks of dosing (intermittent), 22-month follow-up |
| Measures | tryptophan hydroxylase-immunoreactive fiber density, BDNF levels, microglial cell density, astrocyte density |
| Topics | MDMA Serotonin |
| Citations | 21 |
| Key findings | Serotonergic fiber density recovered more fully after intermittent MDMA than after a single dose, and intermittent treatment reduced aberrant fiber clusters in the parietal cortex at 22 months. No differences in microglial or astrocyte densities versus control suggest no accelerated aging or neurodegeneration. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a popular party drug known to cause selective serotonergic damage. Here we examined the long-term recovery and aging of serotonergic fibers and levels of brain-derived neurotrophic factor (BDNF) after intermittent MDMA administration (15 mg kg(-1) i.p. every 7th day for 4 weeks, MDMA ×4) and a single-dose treatment (15 mg kg(-1) i.p., MDMA ×1) in adolescent/young adult male Dark Agouti rats. After MDMA treatment, tryptophan hydroxylase-immunoreactive fiber density decreased and then recovered in all brain regions. Recovery was more pronounced in the MDMA ×4 group compared with the MDMA ×1 group, but similar long-term BDNF responses were found after both treatments. Twenty-two months after treatment, there were fewer clusters of aberrant serotonergic fibers in the parietal cortex in the MDMA ×4 group compared with the MDMA ×1 group. There was no difference in the density of microglial cells or astrocytes in treated groups versus the control 22 months after the treatments. These results indicate that recovery of serotonergic fibers is faster after intermittent MDMA treatment than after single-dose administration, and differences in BDNF levels per se are unlikely to account for this difference. Moreover, it seems that intermittent MDMA treatment attenuates the morphological signs of aging in serotonergic fibers. In addition, neither intermittent nor single-dose MDMA exposition of young animals induces accelerated aging processes or neurodegeneration in senescence, as indicated by the unaltered densities of microglial cells and astrocytes in the treated groups compared with the control.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 9
- 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
- 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
- Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity. Archives of Toxicology July 2018
- Downregulation of the Vitamin D Receptor Regulated Gene Set in the Hippocampus After MDMA Treatment. Frontiers in Pharmacology 2018
and 4 more in the library
Cites 19
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- Reorganization of ascending 5-HT axon projections in animals previously exposed to the recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") Journal of Neuroscience August 1, 1995
- Neurotoxicity of MDMA and Related Compounds: Anatomic Studiesa Annals of the New York Academy of Sciences October 1, 1990
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- 5‐HT loss in rat brain following 3, 4‐methylenedioxymethamphetamine (MDMA), p‐chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine British Journal of Pharmacology March 1, 1993
and 14 more in the library