title: 5-HT1-like receptor agonists enhance wakefulness.
abstract: The effects of four 5-HT1-like receptor agonists (8-OH-DPAT, RU 24969, BEA 1654 and 5-carboxamidotryptamine) and some putative 5-HT1-like receptor antagonists on vigilance were examined in an attempt to clarify the role of 5-HT1-like receptors in the sleep-waking pattern of rats. Both 8-OH-DPAT (0.5-2.0 mg/kg, s.c.) and RU 24969 (0.5-2.0 mg/kg, s.c.) increased wakefulness and the latencies of slow wave and rapid eye movement (REM) sleep. The slow wave and REM sleep were correspondingly decreased or completely abolished. The two other 5-HT1-like receptor agonists had either a slight (BEA 1654, 1.0-5.0 mg/kg, s.c.) or no (5-carboxamidotryptamine, 0.5-2.0 mg/kg, s.c.) effect on sleep pattern. The arousal effect of 8-OH-DPAT was further potentiated in rats pretreated with reserpine (2.5 mg/kg, i.p.; 18 hr before 8-OH-DPAT). The non-selective 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (2.0 mg/kg, i.p.) and the beta-adrenoceptor antagonist propranolol (16.0 mg/kg, s.c.), which is a putative antagonist at 5-HT1A and 5-HT1B receptor subtypes, significantly potentiated the arousal effect of RU 24969. The putative 5-HT1A and 5-HT1B receptor antagonist, cyanopinolol (4.0 mg/kg, s.c.), mixed 5-HT1A receptor agonist/antagonist MDL 72832 (1.0 mg/kg, s.c.) and the alpha 1-adrenoceptor antagonist prazosin (2.0 mg/kg) did not affect the vigilance, altered by RU 24969. These results suggest that the arousal effect of 5-HT1-like receptor agonists is probably not mediated by any of the subtypes of 5-HT1-like receptors or by an activation of a noradrenergic system.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Dzoljic
authors.forename: O E
authors.initials: OE
authors.lastname: Ukponmwan
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; C045007:N-(3-acetylaminophenyl)piperazine