Increased wakefulness, motor activity and decreased theta activity after blockade of the 5‐HT2B receptor by the subtype‐selective antagonist SB‐215505

• Published in: British journal of pharmacology Vol. 142; no. 8; pp. 1332 - 1342
• Main Authors: Kantor, Sandor, Jakus, Rita, Balogh, Brigitta, Benko, Anita, Bagdy, Gyorgy
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2004; Nature Publishing
• Subjects: 5‐HT2B receptor; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; EEG analysis; fast Fourier transformation; Indoles - pharmacology; Male; Medical sciences; motor activity; Motor Activity - drug effects; Motor Activity - physiology; Pharmacology. Drug treatments; Quinolines - pharmacology; Rats; Receptor, Serotonin, 5-HT2B - physiology; SB‐215505; Serotonin; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - pharmacology; sleep; spectral analysis; theta activity; Theta Rhythm - drug effects; vigilance; Wakefulness - drug effects; Wakefulness - physiology; Vigilance; Fourier transformation; Serotonin; fast Fourier transformation; Electrophysiology; Electroencephalography; 5-HT2B receptor; Spectral analysis; motor activity; theta activity; SB-215505; Sleep; EEG analysis; Neurotransmitter; Sleep wake cycle; Antagonist; 5-HT2B serotonin receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705887

Serotonin‐2 receptor antagonists, like ritanserin, greatly enhance deep slow wave sleep (SWS‐2) and low‐frequency EEG power in humans and rodents. 5‐HT2A and 5‐HT2C receptors may be involved in these effects, but the role of the 5‐HT2B receptor is still unclear. To investigate the role of the 5‐HT2B 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. 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). The well‐known SWS‐2 enhancing effect of 5‐HT2 receptor antagonists is mediated by 5‐HT2A and/or 5‐HT2C receptors. In contrast, blockade of 5‐HT2B receptors increases motor activity and W along with decreased theta activity during W and PS. Activation of 5‐HT2B receptors may contribute to initiation of sleep and to theta generation during W and PS under physiological conditions. British Journal of Pharmacology (2004) 142, 1332–1342. doi:10.1038/sj.bjp.0705887