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Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat

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Abstract

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.

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Authors and Affiliations

  1. Department of Neuropsychopharmacology, Janssen Research Foundation, B-2340, Beerse, Belgium

    Christine Dugovic, Albert Wauquier, Roger Marrannes & Paul A. J. Janssen

  2. Department of Biochemical Pharmacology, Janssen Research Foundation, B-2340, Beerse, Belgium

    Josee E. Leysen & Paul A. J. Janssen

Authors
  1. Christine Dugovic
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  2. Albert Wauquier
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  3. Josee E. Leysen
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  4. Roger Marrannes
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  5. Paul A. J. Janssen
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Dugovic, C., Wauquier, A., Leysen, J.E. et al. Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat. Psychopharmacology 97, 436–442 (1989). https://doi.org/10.1007/BF00439544

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  • DOI: https://doi.org/10.1007/BF00439544

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