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Decrease in REM latency and changes in sleep quality parallel serotonergic damage and recovery after MDMA: a longitudinal study over 180 days

Kirilly, Eszter; Molnar, Eszter; Balogh, Brigitta; Kantor, Sandor; Hansson, Stefan LU ; Palkovits, Miklos and Bagdy, Gyorgy (2008) In International Journal of Neuropsychopharmacology 11(6). p.795-809
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,... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
REM, MDMA, median raphe nucleus, depression, dorsal raphe nucleus, latency, serotonin transporter
in
International Journal of Neuropsychopharmacology
volume
11
issue
6
pages
795 - 809
publisher
Cambridge University Press
external identifiers
  • wos:000259706800005
  • scopus:50849127886
ISSN
1469-5111
DOI
10.1017/S1461145708008535
language
English
LU publication?
yes
id
ff5efde6-2fc5-4963-8036-bfe6411bf80d (old id 1286705)
date added to LUP
2009-01-29 15:20:56
date last changed
2017-01-01 04:25:11
@article{ff5efde6-2fc5-4963-8036-bfe6411bf80d,
  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.},
  author       = {Kirilly, Eszter and Molnar, Eszter and Balogh, Brigitta and Kantor, Sandor and Hansson, Stefan and Palkovits, Miklos and Bagdy, Gyorgy},
  issn         = {1469-5111},
  keyword      = {REM,MDMA,median raphe nucleus,depression,dorsal raphe nucleus,latency,serotonin transporter},
  language     = {eng},
  number       = {6},
  pages        = {795--809},
  publisher    = {Cambridge University Press},
  series       = {International Journal of Neuropsychopharmacology},
  title        = {Decrease in REM latency and changes in sleep quality parallel serotonergic damage and recovery after MDMA: a longitudinal study over 180 days},
  url          = {http://dx.doi.org/10.1017/S1461145708008535},
  volume       = {11},
  year         = {2008},
}