Decrease in REM latency and changes in sleep quality parallel serotonergic damage and recovery after MDMA: a longitudinal study over 180 days.
Eszter Kirilly, Eszter Molnár, Brigitta Balogh, Sandor Kantor, Stefan R Hansson, Miklos Palkovits, György Bagdy
The International Journal of Neuropsychopharmacology September 2008 DOI: 10.1017/s1461145708008535 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Longitudinal Peer reviewed |
|---|---|
| Population | Male Dark Agouti rats |
| Intervention | MDMA |
| Dose | 15 mg/kg |
| Duration | 180 days after a single dose |
| Topics | MDMA Serotonin |
| Key findings | A single 15 mg/kg MDMA dose in male Dark Agouti rats caused widespread 30-40% reductions in serotonin transporter density at 7 and 21 days, with recovery by 180 days except in the hippocampus. Sleep alterations, including reduced REM latency and increased fragmentation, also resolved by 180 days. The authors suggest these transient serotonergic and sleep changes resemble EEG sleep features described in depression. |
Abstract
The recreational drug ecstasy [3,4-methylenedioxymethamphetamine (MDMA)], has been found to selectively damage brain serotonin neurons in experimental animals, and probably in human MDMA users, but detailed morphometric analyses and parallel functional measures during damage and recovery are missing. Since there is evidence that serotonin regulates sleep, we have compared serotonergic markers parallel with detailed analysis of sleep patterns at three time-points within 180 d after a single dose of 15 mg/kg MDMA in male Dark Agouti rats. At 7 d and 21 d after MDMA treatment, significant(30-40%), widespread reductions in serotonin transporter (5-HTT) density were detected in the cerebral cortex, hippocampus, most parts of the hypothalamus, and some of the brainstem nuclei. With the exception of the hippocampus, general recovery was observed in the brain 180 d after treatment. Transient increases followed by decreases were detected in 5-HTT mRNA expression of dorsal and median raphe nuclei at 7 d and 21 d after the treatment. Significant reductions in rapid eye movement (REM) sleep latency, increases in delta power spectra in non-rapid eye movement sleep and increased fragmentation of sleep were also detected, but all these alterations disappeared by the 180th day. The present data provide evidence for long-term, albeit, except for the hippocampus, transient changes in the terminal and cellular regions of the serotonergic system after this drug. Reduced REM latency and increased sleep fragmentation are the most characteristic alterations of sleep consistently described in depression using EEG sleep polygraphy.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
- Effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity Journal of Neurochemistry November 30, 2009
- Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat The Journal of Comparative Neurology March 31, 2011
- Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging International Journal of Molecular Sciences June 24, 2022
- 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 5 more in the library
Cites 12
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and 7 more in the library