title: Chronic escitalopram treatment caused dissociative adaptation in serotonin (5-HT) 2C receptor antagonist-induced effects in REM sleep, wake and theta wave activity.
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.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
authors.forename: Diána
authors.initials: D
authors.lastname: Kostyalik
authors.forename: Zita
authors.initials: Z
authors.lastname: Kátai
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.forename: Dorottya
authors.initials: D
authors.lastname: Pap
authors.forename: Péter
authors.initials: P
authors.lastname: Petschner
authors.forename: Eszter
authors.initials: E
authors.lastname: Molnár
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.forename: Lajos
authors.initials: L
authors.lastname: Kalmár
authors.forename: László
authors.initials: L
authors.lastname: Tóthfalusi
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bagdy
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000631:Aminopyridines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004569:Electroencephalography; D004576:Electromyography; D005583:Fourier Analysis; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors; D012895:Sleep, REM / Q000187:drug effects*; D013826:Theta Rhythm / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D000631:Aminopyridines; D015283:Citalopram; D007211:Indoles; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline