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

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.