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Experimental Brain Research

, Volume 232, Issue 3, pp 935–946 | Cite as

Chronic escitalopram treatment caused dissociative adaptation in serotonin (5-HT) 2C receptor antagonist-induced effects in REM sleep, wake and theta wave activity

  • Diána Kostyalik
  • Zita Kátai
  • Szilvia Vas
  • Dorottya Pap
  • Péter Petschner
  • Eszter Molnár
  • István Gyertyán
  • Lajos Kalmár
  • László Tóthfalusi
  • Gyorgy BagdyEmail author
Research Article

Abstract

Several multi-target drugs used in treating psychiatric disorders, such as antidepressants (e.g. agomelatine, trazodone, nefazodone, amitriptyline, mirtazapine, mianserin, fluoxetine) or most atypical antipsychotics, have 5-hydroxytryptamine 2C (5-HT2C) receptor-blocking property. Adaptive changes in 5-HT2C receptor-mediated functions are suggested to contribute to therapeutic effects of selective serotonin reuptake inhibitor (SSRI) antidepressants after weeks of treatment, at least in part. Beyond the mediation of anxiety and other functions, 5-HT2C receptors are involved in sleep regulation. Anxiety-related adaptive changes caused by antidepressants have been studied extensively, although sleep- and electroencephalography (EEG)-related functional studies are still lacking. The aim of this study was to investigate the effects of chronic SSRI treatment on 5-HT2C receptor antagonist-induced functions in different vigilance stages and on quantitative EEG (Q-EEG) spectra. Rats were treated with a single dose of the selective 5-HT2C receptor antagonist SB-242084 (1 mg/kg, i.p.) or vehicle at the beginning of passive phase following a 20-day-long SSRI (escitalopram; 10 mg/kg/day, osmotic minipump) or VEHICLE pretreatment. Fronto-parietal electroencephalogram, electromyogram and motility were recorded during the first 3 h of passive phase. We found that the chronic escitalopram pretreatment attenuated the SB-242084-caused suppression in rapid eye movement sleep (REMS). On the contrary, the 5-HT2C receptor antagonist-induced elevations in passive wake and theta (5–9 Hz) power density during active wake and REMS were not affected by the SSRI. In conclusion, attenuation in certain, but not all vigilance- and Q-EEG-related functions induced by the 5-HT2C receptor antagonist, suggests dissociation in 5-HT2C receptor adaptation.

Keywords

SB-242084 REM sleep Theta waves Functional adaptation Anxiety Depression 

Notes

Acknowledgments

This study was supported by TAMOP-4.2.1. B-09/1/KMR-2010-0001 and by Richter Gedeon Plc.

Conflict of interest

The aforementioned funding agencies did not have any further role in study design, in the collection, analysis and interpretation of data, in writing of the report and in the decision to submit the paper for publication.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Diána Kostyalik
    • 1
  • Zita Kátai
    • 1
  • Szilvia Vas
    • 1
    • 2
  • Dorottya Pap
    • 1
    • 2
  • Péter Petschner
    • 1
    • 2
  • Eszter Molnár
    • 1
  • István Gyertyán
    • 3
  • Lajos Kalmár
    • 4
  • László Tóthfalusi
    • 1
  • Gyorgy Bagdy
    • 1
    • 2
    Email author
  1. 1.Department of PharmacodynamicsSemmelweis UniversityBudapestHungary
  2. 2.MTA-SE, Neuropsychopharmacology and Neurochemistry Research GroupBudapestHungary
  3. 3.Department of Behavioural PharmacologyGedeon Richter Plc.BudapestHungary
  4. 4.Institute of Enzymology, Research Centre for Natural SciencesHungarian Academy of SciencesBudapestHungary

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