Nonphotic Entrainment by 5-HT1A/7Receptor Agonists Accompanied by ReducedPer1andPer2mRNA Levels in the Suprachiasmatic Nuclei

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Abstract
In mammals, the environmental light/dark cycle strongly synchronizes the circadian clock within the suprachiasmatic nuclei (SCN) to 24 hr. It is well known that not only photic but also nonphotic stimuli can entrain the SCN clock. Actually, many studies have shown that a daytime injection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT), a serotonin 1A/7 receptor agonist, as a nonphotic stimulus induces phase advances in hamster behavioral circadian rhythmsin vivo, as well as the neuron activity rhythm of the SCNin vitro. Recent reports suggest that mammalian homologs of theDrosophilaclock gene,Period(Per), are involved in photic entrainment. Therefore, we examined whether phase advances elicited by 8-OH DPAT were associated with a change ofPeriodmRNA levels in the SCN. In this experiment, we cloned partial cDNAs encoding hamsterPer1,Per2, andPer3and observed both circadian oscillation and the light responsiveness ofPeriod. Furthermore, we found that the inhibitory effect of 8-OH DPAT on hamsterPer1andPer2mRNA levels in the SCN occurred only during the hamster's mid-subjective day, but not during the early subjective day or subjective night. The present findings demonstrate that the acute and circadian time-dependent reduction ofPer1and/orPer2mRNA in the hamster SCN by 8-OH DPAT is strongly correlated with the phase resetting in response to 8-OH DPAT.