title: Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains.
abstract: BACKGROUND
  Shortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.
  
  
  RESULTS
  Chronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis. Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5-9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.
  
  
  CONCLUSIONS
  In conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. kostyalik.diana@pharma.semmelweis-univ.hu.
authors.forename: Diána
authors.initials: D
authors.lastname: Kostyalik
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. vas.szilvia@pharma.semmelweis-univ.hu.|MTA-SE, Neuropsychopharmacology and Neurochemistry Research Group, Budapest, Hungary. vas.szilvia@pharma.semmelweis-univ.hu.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. kataizita@gmail.com.
authors.forename: Zita
authors.initials: Z
authors.lastname: Kátai
authors.affiliation: Department of Neurophysiology, Gedeon Richter Plc., Gyömrői út 19-21, Budapest, Hungary. t.kitka@richter.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kitka
authors.affiliation: Department of Behavioural Pharmacology, Gedeon Richter Plc., Gyömrői út 19-21, Budapest, Hungary. i.gyertyan@richter.hu.
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. bagdy.gyorgy@pharma.semmelweis-univ.hu.|MTA-SE, Neuropsychopharmacology and Neurochemistry Research Group, Budapest, Hungary. bagdy.gyorgy@pharma.semmelweis-univ.hu.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bagdy
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. tothfalusi.laszlo@pharma.semmelweis-univ.hu.
authors.forename: László
authors.initials: L
authors.lastname: Tóthfalusi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002408:Catheters, Indwelling; D015283:Citalopram / Q000494:pharmacology*; D004567:Electrodes, Implanted; D004569:Electroencephalography; D008297:Male; D008390:Markov Chains; D008959:Models, Neurological; D017286:Polysomnography; D011897:Random Allocation; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors