Serotonin 1A-mediated amplification of light-induced phase advances of circadian rhythms in the Syrian hamster: Post-light effects

Abstract

Certain serotonergic compounds that have an agonist/antagonist activity at the 5-HT 1A receptor subtype are known to greatly potentiate the ability of light to advance the phase of circadian activity rhythms in hamsters. Typically, investigational compounds are injected 30 min to 1 h prior to a phase-advancing light pulse, and it is not known if these compounds are efficacious when injected after a short light pulse. In this study we injected the 5-HT 1A mixed agonist/antagonist BMY 7378 from 1 to 7 h after a short phase advancing light pulse at CT 19 in hamsters to assess the temporal window of efficacy of this compound. BMY 7378 effectively doubles the magnitude of light-induced phase advances in hamster circadian wheel running rhythms for 6 h after a light pulse administered at CT 19, and this effect abruptly ends at 7 h post-light. This demonstrates that the molecular events initiated by a light pulse at CT 19 responsible for initiating phase advances in circadian activity rhythms can be modulated for at least the next 6 h in the hamster. However, this effect found with BMY 7378 does not extend to all serotonergic compounds as the inhibitory activity of 8-OH-DPAT on light-induced phase advances is not apparent when injected just 3 h after a light pulse. Since BMY 7378 can elicit such major shifts in the timing of the circadian clock it should be useful as a tool to explore potential changes in gene expression that lead to phase shifts in circadian rhythms, now known to be susceptible to modification for 6 h after a phase-advancing light pulse.