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

Jul 26, 2000The Journal of neuroscience : the official journal of the Society for Neuroscience

Non-light signals that reset the body clock involve 5-HT1A/7 receptors and lower key clock gene activity in the brain's time-keeping center

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Abstract

The serotonin receptor agonist 8-OH DPAT induces a circadian phase advance in hamsters associated with changes in Period gene expression.

8-OH DPAT administration during the mid-subjective day results in phase advances in hamster circadian rhythms.
The treatment leads to a reduction in mRNA levels of the Period genes Per1 and Per2 in the suprachiasmatic nuclei.
This inhibitory effect on Period gene expression is not observed during the early subjective day or subjective night.
Changes in Period mRNA levels correspond with the timing of the phase resetting induced by 8-OH DPAT.

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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 rhythms in vivo, as well as the neuron activity rhythm of the SCN in vitro. Recent reports suggest that mammalian homologs of the Drosophila clock gene, Period (Per), are involved in photic entrainment. Therefore, we examined whether phase advances elicited by 8-OH DPAT were associated with a change of Period mRNA levels in the SCN. In this experiment, we cloned partial cDNAs encoding hamster Per1, Per2, and Per3 and observed both circadian oscillation and the light responsiveness of Period. Furthermore, we found that the inhibitory effect of 8-OH DPAT on hamster Per1 and Per2 mRNA 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 of Per1 and/or Per2 mRNA in the hamster SCN by 8-OH DPAT is strongly correlated with the phase resetting in response to 8-OH DPAT.

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

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