Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat.
Recently developed agents specifically acting on different 5-hydroxytryptamine (5-HT) receptor populations were used to analyze the functional role of 5-HT2 receptor subtypes in the sleep-wakefulness cycle of the rat. The 5-HT2 receptor antagonist ritanserin injected intraperitoneally (IP) (0.04-2.5 mg/kg) induced an increase in deep slow wave sleep (SWS2) duration at the expense of wakefulness (W), light slow wave sleep (SWS1) and paradoxical sleep (PS). The stimulation of 5-HT2 receptors by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced a dose-related increase in W and a dose-dependent decrease in both SWS2 and PS. Pretreatment with ritanserin (0.16-2.5 mg/kg) or with cinanserin (2.5-5 mg/kg), another 5-HT2 receptor antagonist, dose-dependently reversed the W enhancement and the SWS2 deficit produced by DOM, but not the PS deficit. Sleep-wakefulness alterations (increase in W and SWS1 combined with a suppression of SWS2 and PS) observed after IP injection of two putative 5-HT1 receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (2.5 mg/kg) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) (0.63 mg/kg), were not modified by ritanserin pretreatment (0.16-2.5 mg/kg). These results further support the hypothesis that the serotonergic system plays an active role in the regulation of the sleep-wakefulness cycle in the rat and that 5-HT2 receptors are involved in this action. In addition, it is suggested that 5-HT1 receptor subtypes are unlikely to interact with 5-HT2 receptors in the sleep-wakefulness modulation mediated through 5-HT2 receptors.
Dugovic
C
C
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
Wauquier
A
A
Leysen
J E
JE
Marrannes
R
R
Janssen
P A
PA
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D002928:Cinanserin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin; D012890:Sleep / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology*
D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002928:Cinanserin