title: Ghrelin receptor-knockout mice display alterations in circadian rhythms of activity and feeding under constant lighting conditions.
abstract: Ghrelin is an orexigenic hormone produced by the stomach. Ghrelin, however, may also be a modulator of the circadian system given that ghrelin receptors are expressed in the master clock, the suprachiasmatic nucleus (SCN) and several outputs of this region. To investigate this, we performed analyses of running wheel activity and neuronal activation in wild type (WT) and growth hormone secretagogue receptor-knockout (GHSR-KO) mice under various lighting conditions. GHSR-KO and WT mice were maintained under constant dark (DD) or constant light (LL) with ad libitum access to food before being placed on a schedule of temporally restricted access to food (4 h/day) for 2 weeks. There were no differences between KO and WT mice in free-running period under DD, but GHSR-KO mice required more days to develop a high level of food anticipatory activity, and this was lower than that observed in WT mice. Under LL, GHSR-KO mice showed greater activity overall, lengthening of their circadian period, and more resistance to the disorganisational effects of LL. Furthermore, GHSR-KO mice showed greater activity overall, and greater activity in anticipation of a scheduled meal under LL. These behavioral effects were not correlated with changes in the circadian expression of the Fos, Per1 or Per2 proteins under any lighting conditions. These results suggest that the ghrelin receptor plays a role in modulating the activity of the circadian system under normal conditions and under restricted feeding schedules, but does so through mechanisms that remain to be determined.
authors.affiliation: Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada; Department of Psychology, Thompson Rivers University, Kamloops, BC, Canada.
authors.forename: E Waddington
authors.initials: EW
authors.lastname: Lamont
authors.forename: J
authors.initials: J
authors.lastname: Bruton
authors.forename: I D
authors.initials: ID
authors.lastname: Blum
authors.forename: A
authors.initials: A
authors.lastname: Abizaid
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological / Q000502:physiology; D001921:Brain / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D006799:Housing, Animal; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D056950:Period Circadian Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos; D054440:Receptors, Ghrelin
keywords: arcuate nucleus of the hypothalamus; dorsomedial nucleus of the hypothalamus; growth hormone secretagogue receptor; lateral hypothalamus; para-ventricular nucleus of the hypothalamus; suprachiasmatic nucleus