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Effect of MT 1 melatonin receptor deletion on melatonin‐mediated phase shift of circadian rhythms in the C57BL/6 mouse
Author(s) -
Dubocovich M. L.,
Hudson R. L.,
Sumaya I. C.,
Masana M. I.,
Manna E.
Publication year - 2005
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2005.00230.x
Subject(s) - melatonin , circadian rhythm , medicine , suprachiasmatic nucleus , endocrinology , light effects on circadian rhythm , melatonin receptor , receptor , biology , rhythm , knockout mouse
In the mouse suprachiasmatic nucleus (SCN), melatonin activates MT 1 and MT 2 G‐protein coupled receptors, which are involved primarily in inhibition of neuronal firing and phase shift of circadian rhythms. This study investigated the ability of melatonin to phase shift circadian rhythms in wild type (WT) and MT 1 melatonin receptor knockout (KO) C57BL/6 mice. In WT mice, melatonin (90 μ g/mouse, s.c.) administered at circadian time 10 (CT10; CT12 onset of activity) significantly phase advanced the onset of the circadian activity rhythm (0.60 ± 0.09 hr, n = 41) when compared with vehicle treated controls (−0.02 ± 0.07 hr, n = 28) ( P < 0.001). In contrast, C57 MT 1 KO mice treated with melatonin did not phase shift circadian activity rhythms (−0.10 ± 0.12 hr, n = 42) when compared with vehicle treated mice (−0.12 ± 0.07 hr, n = 43). Similarly, in the C57 MT 1 KO mouse melatonin did not accelerate re‐entrainment to a new dark onset after an abrupt advance of the dark cycle. In contrast, melatonin (3 and 10 p m ) significantly phase advanced circadian rhythm of neuronal firing in SCN brain slices independent of genotype with an identical maximal shift at 10 p m (C57 WT: 3.61 ± 0.38 hr, n = 3; C57 MT 1 KO: 3.45 ± 0.11 hr, n = 4). Taken together, these results suggest that melatonin‐mediated phase advances of circadian rhythms of neuronal firing in the SCN in vitro may involve activation of the MT 2 receptor while in vivo activation of the MT 1 and possibly the MT 2 receptor may be necessary for the expression of melatonin‐mediated phase shifts of overt circadian activity rhythms.