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 language | English |
|---|---|
| Pages (from-to) | 1332-1342 |
| Number of pages | 11 |
| Journal | British Journal of Pharmacology |
| Volume | 142 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - aug. 2004 |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT 2B receptor by the subtype-selective antagonist SB-215505. / Kantor, Sandor; Jakus, R.; Balogh, Brigitta; Benko, Anita; Bagdy, G.
In: British Journal of Pharmacology, Vol. 142, No. 8, 08.2004, p. 1332-1342.Research output: Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=4444319543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4444319543&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0705887
DO - 10.1038/sj.bjp.0705887
M3 - Article
C2 - 15265808
AN - SCOPUS:4444319543
VL - 142
SP - 1332
EP - 1342
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 8
ER -