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.

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

“…Kostyalik et al have described that SB-242084 elevated PW duration, and suppressed REMS which effect was attenuated by chronic ESC pretreatment, in rats. Regarding qEEG, they have found enhanced theta power during AW and also during REMS that was not further modified by chronic escitalopram pretreatment (Kostyalik et al, 2014). The thetaenhancing effect of the 5-HT 2C R-antagonist and thus the role of 5-HT 2C R in the regulation of theta activity have been supported by Hajos et al (2003b).…”

“…Importantly, Kantor et al have demonstrated that although 0.3 and 1.0 mg/kg doses of the drug produced similar anxiolytic effects, only the higher dose affected the sleep-wake architecture prominently (wake-promoting effect with reduction of SWS-2), in Sprague-Dawley rats (Kantor et al, 2005). A REMS-reducing effect have been found at 1 mg/kg dose in Wistar rats, and theta power elevations during AW and REMS have also been observed following this treatment (Kostyalik et al, 2014).…”

Brain bioelectrical activity changes in patients with poststroke depression and apathy

“…В контрольной группе они, возможно, носят ком-пенсаторный характер. В группах с постинсультной депрес-сией и апатией изменения в быстром частотном диапазоне ЭЭГ могут отражать дисбаланс в функционировании меди-аторных систем [20,21]. Через 12 мес также были получены противоположно направленные корреляции индекса бета 2-активности с по-казателями неврологического дефицита по шкале NIHSS в контрольной (отрицательные) и основной (положитель-ные) группах (см.…”

Additive effect of 5-HT2C and CB1 receptor blockade on the regulation of sleep–wake cycle

“…Injections of ritanserin and ketanserin, possessing 5-HT 2A/2C receptor antagonist properties, induced a significant increase in SWS and a reduction of both REMS and wakefulness in rats [19–23]. However, our previous data show that SB-242084, a highly selective 5-HT 2C receptor antagonist, promotes wakefulness while decreases both deep slow wave sleep (SWS-2) and REMS [24, 25].…”