title: Decreased plasma ghrelin contributes to anorexia following novelty stress.
abstract: We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B)/(2C) receptors (5-HT(1B)/(2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B)/(2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B)/(2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.
authors.affiliation: Department of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Muto
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sadakane
authors.forename: Miwa
authors.initials: M
authors.lastname: Nahata
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D000818:Animals; D000855:Anorexia / Q000097:blood* / Q000209:etiology; D001066:Appetite / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D054439:Ghrelin / Q000097:blood*; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood* / Q000150:complications
chemical_list: D054439:Ghrelin; D044105:Receptor, Melanocortin, Type 4; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D018019:Receptors, Corticotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone