Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT 2B receptor by the subtype-selective antagonist SB-215505

Sandor Kantor, R. Jakus, Brigitta Balogh, Anita Benko, G. Bagdy

Research output: Article

41 Citations (Scopus)

Abstract

1. Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT 2A and 5-HT 2C receptors may be involved in these effects, but the role of the 5-HT 2B receptor is still unclear. 2. To investigate the role of the 5-HT 2B receptor in regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505 (0.1, 0.3 and 1.0 mg kg -1 i.p.) was administered to Sprague-Dawley rats at light onset (beginning of passive phase). EEG, EMG and motor activity were recorded during the subsequent 8 h. 3. SB-215505 dose-dependently increased wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly increased motor activity was found. Spectral analysis of the EEG in W showed a dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low-frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505 treatment. In PS, the drug dose-dependently decreased EEG power solely in the theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). 4. The well-known SWS-2 enhancing effect of 5-HT 2 receptor antagonists is mediated by 5-HT 2A and/or 5-HT 2C receptors. In contrast, blockade of 5-HT 2B receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5-HT 2B receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions.

Original languageEnglish
Pages (from-to)1332-1342
Number of pages11
JournalBritish Journal of Pharmacology
Volume142
Issue number8
DOIs
Publication statusPublished - aug. 2004

Fingerprint

Receptor, Serotonin, 5-HT2B
Wakefulness
REM Sleep
Electroencephalography
Sleep
Motor Activity
Serotonin 5-HT2 Receptors
Receptor, Serotonin, 5-HT2C
Serotonin
Ritanserin
Light
Serotonin Antagonists
Sleep Stages
Pharmaceutical Preparations
Sprague Dawley Rats
Rodentia
SB 215505
Power (Psychology)

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT 2B receptor by the subtype-selective antagonist SB-215505",
abstract = "1. Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT 2A and 5-HT 2C receptors may be involved in these effects, but the role of the 5-HT 2B receptor is still unclear. 2. To investigate the role of the 5-HT 2B receptor in regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505 (0.1, 0.3 and 1.0 mg kg -1 i.p.) was administered to Sprague-Dawley rats at light onset (beginning of passive phase). EEG, EMG and motor activity were recorded during the subsequent 8 h. 3. SB-215505 dose-dependently increased wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly increased motor activity was found. Spectral analysis of the EEG in W showed a dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low-frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505 treatment. In PS, the drug dose-dependently decreased EEG power solely in the theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). 4. The well-known SWS-2 enhancing effect of 5-HT 2 receptor antagonists is mediated by 5-HT 2A and/or 5-HT 2C receptors. In contrast, blockade of 5-HT 2B receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5-HT 2B receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions.",
keywords = "5-HT receptor, EEG analysis, Fast Fourier transformation, Motor activity, SB-215505, Serotonin, Sleep, Spectral analysis, Theta activity, Vigilance",
author = "Sandor Kantor and R. Jakus and Brigitta Balogh and Anita Benko and G. Bagdy",
year = "2004",
month = "8",
doi = "10.1038/sj.bjp.0705887",
language = "English",
volume = "142",
pages = "1332--1342",
journal = "British Journal of Pharmacology",
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T1 - Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT 2B receptor by the subtype-selective antagonist SB-215505

AU - Kantor, Sandor

AU - Jakus, R.

AU - Balogh, Brigitta

AU - Benko, Anita

AU - Bagdy, G.

PY - 2004/8

Y1 - 2004/8

N2 - 1. Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT 2A and 5-HT 2C receptors may be involved in these effects, but the role of the 5-HT 2B receptor is still unclear. 2. To investigate the role of the 5-HT 2B receptor in regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505 (0.1, 0.3 and 1.0 mg kg -1 i.p.) was administered to Sprague-Dawley rats at light onset (beginning of passive phase). EEG, EMG and motor activity were recorded during the subsequent 8 h. 3. SB-215505 dose-dependently increased wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly increased motor activity was found. Spectral analysis of the EEG in W showed a dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low-frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505 treatment. In PS, the drug dose-dependently decreased EEG power solely in the theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). 4. The well-known SWS-2 enhancing effect of 5-HT 2 receptor antagonists is mediated by 5-HT 2A and/or 5-HT 2C receptors. In contrast, blockade of 5-HT 2B receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5-HT 2B receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions.

AB - 1. Serotonin-2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS-2) and low-frequency EEG power in humans and rodents. 5-HT 2A and 5-HT 2C receptors may be involved in these effects, but the role of the 5-HT 2B receptor is still unclear. 2. To investigate the role of the 5-HT 2B receptor in regulation of the sleep-wake cycle, the subtype-selective antagonist SB-215505 (0.1, 0.3 and 1.0 mg kg -1 i.p.) was administered to Sprague-Dawley rats at light onset (beginning of passive phase). EEG, EMG and motor activity were recorded during the subsequent 8 h. 3. SB-215505 dose-dependently increased wakefulness (W) at the expense of the intermediate stage of sleep, paradoxical sleep (PS) and SWS-2 in the first hour. Parallel to increased W, significantly increased motor activity was found. Spectral analysis of the EEG in W showed a dose-dependent decrease in power density in the 3-8 Hz frequency range (maximum effect at 6 Hz). In light slow wave sleep and SWS-2, the drug reduced low-frequency (<8 Hz) EEG power, suggesting decreased sleep intensity after SB-215505 treatment. In PS, the drug dose-dependently decreased EEG power solely in the theta (6-9 Hz) band, primarily affecting the peak power value (7 Hz). 4. The well-known SWS-2 enhancing effect of 5-HT 2 receptor antagonists is mediated by 5-HT 2A and/or 5-HT 2C receptors. In contrast, blockade of 5-HT 2B receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5-HT 2B receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions.

KW - 5-HT receptor

KW - EEG analysis

KW - Fast Fourier transformation

KW - Motor activity

KW - SB-215505

KW - Serotonin

KW - Sleep

KW - Spectral analysis

KW - Theta activity

KW - Vigilance

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