Circadian periods of sensitivity for ramelteon on the onset of running-wheel activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in C3HHeN mice

Rawashdeh, Oliver, Hudson, Randall L., Stepien, Iwona and Dubocovich, Margarita L. (2011) Circadian periods of sensitivity for ramelteon on the onset of running-wheel activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in C3HHeN mice. Chronobiology International, 28 1: 31-38. doi:10.3109/07420528.2010.532894


Author Rawashdeh, Oliver
Hudson, Randall L.
Stepien, Iwona
Dubocovich, Margarita L.
Title Circadian periods of sensitivity for ramelteon on the onset of running-wheel activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in C3HHeN mice
Journal name Chronobiology International   Check publisher's open access policy
ISSN 0742-0528
1525-6073
Publication date 2011
Year available 2010
Sub-type Article (original research)
DOI 10.3109/07420528.2010.532894
Open Access Status Not Open Access
Volume 28
Issue 1
Start page 31
End page 38
Total pages 8
Place of publication Abingdon, Oxfordshire, United Kingdom
Publisher Taylor & Francis
Language eng
Formatted abstract
Ramelteon, an MT1MT2 melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3HHeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90gmouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3HHeN mice. The PRC for ramelteon resembles that for melatonin in C3HHeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6±0.29h, n3) and at CT2 phase delays (-3.2±0.12h, n6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7±0.15h, n4, p<.05; CT2: -1.13±0.08h, n6, p<.001, respectively). The phase shifts induced by both melatonin and ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon showed identical periods of circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro.
Keyword Circadian rhythms
Melatonin
Melatonin receptors
Phase response curve
Ramelteon
Suprachiasmatic nucleus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Wed, 16 Mar 2016, 08:53:17 EST by Oliver Rawashdeh on behalf of Learning and Research Services (UQ Library)