Differential influence of selective 5-HT5A vs 5-HT1A , 5-HT1B , or 5-HT2C receptor blockade upon light-induced phase shifts in circadian activity rhythms: Interaction studies with citalopram

• Published in: European neuropsychopharmacology Vol. 19; no. 12; pp. 887 - 897
• Main Authors: Gannon, Robert L, Peglion, Jean-Louis, Millan, Mark J
• Format: Journal Article
• Language: English
• Published: Netherlands 01.12.2009
• Subjects: Animals; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Circadian Rhythm - radiation effects; Citalopram - pharmacology; Cricetinae; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Internal Medicine; Light; Male; Mesocricetus; Psychiatry; Receptors, Serotonin - classification; Receptors, Serotonin - metabolism; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Time Factors; Suprachiasmatic nucleus; Biological rhythms; Selective serotonin reuptake inhibitors; Raphe nucleus; Serotonin receptors
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2009.06.011

Abstract Though serotonergic mechanisms modulate circadian rhythms, roles of individual serotonin (5-HT) receptors remain uncertain since data are lacking for antagonists. Herein, both the 5-HT5A receptor antagonist, A843277 (10 mg/kg), and the 5-HT1B antagonist, SB224289 (1 mg/kg), inhibited light-induced phase advances in hamster circadian wheel-running rhythms. Conversely, though 5-HT1A and 5-HT7 receptors are likewise implicated in circadian scheduling, their blockade by WAY100635 (0.5 mg/kg) and SB269970 (1 mg/kg), respectively, was ineffective. Since actions of 5-HT reuptake inhibitors are modified by antagonists, we evaluated their influence on suppression of phase advances by citalopram (10 mg/kg). Its action was potentiated by WAY100635 and the 5-HT2C antagonist, SB242084 (1 mg/kg), but not by A842377, SB224289, SB269970, and antagonists at 5-HT2A (MDL100907) and 5-HT6 (SB399885) receptors. In conclusion, this is the first in vivo evidence for an influence of 5-HT5A receptors upon circadian rhythms, but no single class of 5-HT receptor mediates their control by citalopram.