title: Decrease in REM latency and changes in sleep quality parallel serotonergic damage and recovery after MDMA: a longitudinal study over 180 days.
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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Kirilly
authors.forename: Eszter
authors.initials: E
authors.lastname: Molnar
authors.forename: Brigitta
authors.initials: B
authors.lastname: Balogh
authors.forename: Sandor
authors.initials: S
authors.lastname: Kantor
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Hansson
authors.forename: Miklos
authors.initials: M
authors.lastname: Palkovits
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bagdy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006213:Hallucinogens / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D012895:Sleep, REM / Q000187:drug effects*; D013057:Spectrum Analysis; D013997:Time Factors
chemical_list: D006213:Hallucinogens; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine