PMID- 21182402
OWN - NLM
STAT- MEDLINE
DCOM- 20110426
LR  - 20220309
IS  - 1525-6073 (Electronic)
IS  - 0742-0528 (Print)
IS  - 0742-0528 (Linking)
VI  - 28
IP  - 1
DP  - 2011 Feb
TI  - Circadian periods of sensitivity for ramelteon on the onset of running-wheel 
      activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in 
      C3H/HeN mice.
PG  - 31-8
LID - 10.3109/07420528.2010.532894 [doi]
AB  - Ramelteon, an MT(1)/MT(2) 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 C3H/HeN 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 
      (90 microg/mouse, 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 
      C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/HeN mice, 
      showing the same magnitude of maximal shifts at CT10 and CT2, except that the 
      range of sensitivity for ramelteon (CT8-CT12) during the subjective day is 
      broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) 
      administered at CT10 phase advances (5.6 +/- 0.29 h, n = 3) and at CT2 phase delays 
      (-3.2 +/- 0.12 h, n = 6) 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 +/- 0.15 h, n = 4, p < .05; CT2: -1.13 +/- 0.08 h, 
      n = 6, 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.
FAU - Rawashdeh, Oliver
AU  - Rawashdeh O
AD  - Department of Molecular Pharmacology and Biological Chemistry, Northwestern 
      University Feinberg School of Medicine, Northwestern University, Chicago, 
      Illinois, USA.
FAU - Hudson, Randall L
AU  - Hudson RL
FAU - Stepien, Iwona
AU  - Stepien I
FAU - Dubocovich, Margarita L
AU  - Dubocovich ML
LA  - eng
GR  - R01 MH042922/MH/NIMH NIH HHS/United States
GR  - R01 MH042922-18/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Chronobiol Int
JT  - Chronobiology international
JID - 8501362
RN  - 0 (Indenes)
RN  - 0 (Receptors, Melatonin)
RN  - 901AS54I69 (ramelteon)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Circadian Rhythm/*drug effects/*physiology
MH  - Indenes/*pharmacology/therapeutic use
MH  - Male
MH  - Melatonin/pharmacology/physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Motor Activity/drug effects/*physiology
MH  - Receptors, Melatonin/agonists
MH  - *Running
MH  - Sleep Initiation and Maintenance Disorders/drug therapy
MH  - Suprachiasmatic Nucleus/drug effects/*physiology
PMC - PMC5040068
MID - NIHMS308417
EDAT- 2010/12/25 06:00
MHDA- 2011/04/27 06:00
PMCR- 2016/09/28
CRDT- 2010/12/25 06:00
PHST- 2010/12/25 06:00 [entrez]
PHST- 2010/12/25 06:00 [pubmed]
PHST- 2011/04/27 06:00 [medline]
PHST- 2016/09/28 00:00 [pmc-release]
AID - 10.3109/07420528.2010.532894 [doi]
PST - ppublish
SO  - Chronobiol Int. 2011 Feb;28(1):31-8. doi: 10.3109/07420528.2010.532894.