5-HT antagonists suppress sleep and delay its restoration after 5-HTP in p-chlorophenylalanine-pretreated cats.

When injected intraperitoneally (i.p.) into normal cats, methiothepin (1-7.5 mg/kg) or metergoline (0.5-8 mg/kg) induced total insomnia. The duration of suppression of deep slow-wave sleep (SWS2) and paradoxical sleep (PS) was dose-related for methiothepin (10-30 h), but was shorter and not dose-related for metergoline (3-5 h). When injected into the fourth ventricle, methiothepin (20 microgram) induced a selective suppression of PS for 6-7 h). In rho-chlorophenyl-alanine (PCPA)-pretreated, insomniac cats, i.p. injection of 5 mg/kg of DL-5-hydroxytryptophan(5-HTP) was followed by SWS and PS after latencies of 25 and 62 min. When methiothepin (2.5 mg/kg) or metergoline (4 mg/kg) were given before 5-HTP, the latency for the first PS episode increased dramatically to 7 h. Thereafter PS occurred periodically for 10 h but no SWS appeared. These results suggest that a 'PS factor' induced by 5-HTP and different from indolamines is preserved during the antagonistic effect of methiothepin or metergoline until it can act upon the executive mechanisms of PS. Our data also suggest that metergoline and methiothepin suppress but do not delay the mechanism responsible for SWS2 in the PCPA-5-HTP paradigm.