Suppressant effects of selective 5-HT2 antagonists on rapid eye movement sleep in rats.
The effects of the novel, highly selective serotonin-2 (5-HT2) antagonists, ICI 169,369 and ICI 170,809, on 24 h EEG sleep-wake activity were studied in the rat. Both compounds caused a dose-related increase in the latency to rapid eye movement sleep (REMS) and significantly suppressed cumulative REMS time up to 12 h postinjection. In contrast, neither drug disrupted slow-wave sleep continuity in as much as the latency to non-REMS (NREMS) and cumulative NREMS time were unchanged. However, at the highest dose tested (20 mg/kg) ICI 170,809 did produce a significant increase in total NREMS time during the second half of the sleep-awake cycle. These results demonstrate effects of selective 5-HT2 antagonists on sleep in rats which appear to be specific for REMS behavior, suggesting that the priming influence of serotonin on REMS may involve 5-HT2 receptor subtypes. The relationship between the REMS suppressant actions of these compounds and their consideration as therapeutic agents in depression is discussed.
Tortella
F C
FC
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307.
Echevarria
E
E
Pastel
R H
RH
Cox
B
B
Blackburn
T P
TP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology
D011804:Quinolines; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline