WAY-100635, a specific 5-HT1A antagonist, can increase the responsiveness of the mammalian circadian pacemaker to photic stimuli

Mammalian circadian rhythms are synchronized daily to light-dark cycles in the environment. The suprachiasmatic nucleus (SCN) is the proposed site of the major circadian pacemaker. Daily entrainment is believed to be influenc ed by inputs to the SCN, one of these being the dense serotonergic (5-HT) p rojection from the raphe nuclei. WAY-100635 is a potent and selective 5-HT1 A receptor antagonist. In this study, the effects of WAY-100635 on phase-sh ifts of the hamster circadian pacemaker to light were investigated. Phase-d elays after a light pulse administered during the early subjective night (1 5 min at CT14) were observed to be significantly greater following pre-trea tment with WAY-100635 compared to tight pulse alone (P < 0.05). However, pr e-treatment with WAY-100635 had no effect on the magnitude of phase-shifts to light at CT18, late in the subjective night. Serotonin may influence the responsiveness of the circadian pacemaker to photic stimuli. Specifically, WAV-100635 administered at CT14 can augment phase-shifts to light. (C) 200 1 Elsevier Science Ireland Ltd, All rights reserved.