Serotonergic antagonists impair arousal-induced phase shifts of the circadian system of the Syrian hamster

Single episodes of arousal of Syrian hamsters 2 h before projected activity onset (i.e., CT 10) phase-advanced their free-running circadian rhythm of wheel-running. Serial arousal once every 23 h or once every 23.5 h for 7 days caused large composite phase-advances to the wheel-running rhythm, the latter period being more effective in supporting an interval of stable entrainment. Pre-treatment of hamsters at CT 6 with the serotonergic antagonist ritanserin (1-5 mg/kg), which acts at both 5-HT2 and the putative 5-HT7 receptor, impaired the phase-advancing response to arousal at CT 10 but the drug was without effect on phase advances induced by exposure to light. Pre-treatment with a second serotonergic antagonist, ketanserin (1-5 mg/kg), which is without effect at 5-HT7 but has high affinity for 5-HT2 receptors, was also effective in attenuating the phase advancing effect of arousal at CT 10. However, neither agent was able to achieve complete blockade of the phase advances. These results are discussed in relation to in vitro and in vivo studies in the rat which have identified a role for 5-HT7 receptors in serotonin-mediated circadian entrainment.