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

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 i...

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Bibliographic Details
Published in:Experimental brain research 2014-03, Vol.232 (3), p.935-946
Main Authors: Kostyalik, Diána, Kátai, Zita, Vas, Szilvia, Pap, Dorottya, Petschner, Péter, Molnár, Eszter, Gyertyán, István, Kalmár, Lajos, Tóthfalusi, László, Bagdy, Gyorgy
Format: Article
Language:English
Subjects:
Adaptation
Adaptation, Physiological - drug effects
Adaptations
Aminopyridines - pharmacology
Analysis of Variance
Animals
Antidepressants
Anxiety
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Brain research
Citalopram - pharmacology
Drug dosages
Electroencephalography
Electromyography
Eye movements
Fourier Analysis
Fundamental and applied biological sciences. Psychology
Indoles - pharmacology
Laboratory animals
Male
Neurology
Neurosciences
Psychotropic drugs
Rats
Rats, Wistar
Reaction Time - drug effects
Receptors
Research Article
Serotonin
Serotonin Antagonists - pharmacology
Serotonin Uptake Inhibitors
Sleep deprivation
Sleep, REM - drug effects
Sleep. Vigilance
Theta Rhythm - drug effects
Vertebrates: nervous system and sense organs
Wakefulness - drug effects
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Summary: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.
ISSN:0014-4819
1432-1106
DOI:10.1007/s00221-013-3806-8