Differential adaptation of REM sleep latency, intermediate stage and theta power effects of escitalopram after chronic treatment.
The effects of the widely used selective serotonin reuptake inhibitor (SSRI) antidepressants on sleep have been intensively investigated. However, only a few animal studies examined the effect of escitalopram, the more potent S-enantiomer of citalopram, and conclusions of these studies on sleep architecture are limited due to the experimental design. Here, we investigate the acute (2 and 10 mg/kg, i.p. injected at the beginning of the passive phase) or chronic (10 mg/kg/day for 21 days, by osmotic minipumps) effects of escitalopram on the sleep and quantitative electroencephalogram (EEG) of Wistar rats. The first 3 h of EEG recording was analyzed at the beginning of passive phase, immediately after injections. The acutely injected 2 and 10 mg/kg and the chronically administered 10 mg/kg/day escitalopram caused an approximately three, six and twofold increases in rapid eye movement sleep (REMS) latency, respectively. Acute 2-mg/kg escitalopram reduced REMS, but increased intermediate stage of sleep (IS) while the 10 mg/kg reduced both. We also observed some increase in light slow wave sleep and passive wake parallel with a decrease in deep slow wave sleep and theta power in both active wake and REMS after acute dosing. Following chronic treatment, only the increase in REMS latency remained significant compared to control animals. In conclusion, adaptive changes in the effects of escitalopram, which occur after 3 weeks of treatment, suggest desensitization in the function of 5-HT(1A) and 5-HT(1B) receptors.
Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4, 1089, Budapest, Hungary.
Szilvia
S
Vas
Zita
Z
Kátai
Diána
D
Kostyalik
Dorottya
D
Pap
Eszter
E
Molnár
Péter
P
Petschner
Lajos
L
Kalmár
György
G
Bagdy
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography; D004576:Electromyography; D005133:Eye Movements / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects*; D013826:Theta Rhythm / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors