Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT2B receptor by the subtype-selective antagonist SB-215505.
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. 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. 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-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.
Kantor
Sandor
S
Laboratory of Neurochemistry and Experimental Medicine, Semmelweis University National Institute of Psychiatry and Neurology, Budapest, Huvosvolgyi ut 116, H-1021, Hungary.
Jakus
Rita
R
Balogh
Brigitta
B
Benko
Anita
A
Bagdy
Gyorgy
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D044403:Receptor, Serotonin, 5-HT2B / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013826:Theta Rhythm / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D007211:Indoles; D011804:Quinolines; D044403:Receptor, Serotonin, 5-HT2B; C118948:SB 215505; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists