title: Serotonin 2C receptor antagonism ameliorates novelty-induced hypophagia in aged mice.
abstract: This study was conducted to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) 2C receptor (5-HT2CR) signaling during novelty-induced hypophagia in aged mice. Male C57BL/6J mice [6-week-old (young) and 79-80-week-old (aged) mice] were exposed to a novel environment, and its effects on feeding behavior, stress hormones, and appetite-related factors were examined. Exposure of aged mice to a novel environment suppressed food intake and increased corticosterone secretion. These responses were marked compared with those in young mice. The expression in hypothalamic corticotropin-releasing factor (CRF), pituitary CRF1R and proopiomelanocortin mRNA in aged mice exposed to a novel environment was increased or tended to increase, compared to control mice. 5-HT2CR antagonist, SB242084 or rikkunshito administration attenuated the decrease in food intake and increased stress hormone levels in aged mice exposed to the environmental change. The 5-HT2CR mRNA expression in paraventricular nucleus was significantly enhanced, when aged mice was exposure to the novel environment. Thus, novelty-induced hypophagia in aged mice resulted, at least in part, from up-regulated hypothalamic 5-HT2CR function. In conclusion, 5-HT2CR signaling enhancement and the subsequent activation of the CRF neuron were involved in novelty-induced hypophagia in aged mice, and the 5-HT2CR antagonists offer a promising therapeutic option for depression.
authors.affiliation: Tsumura & Co., Tsumura Research Laboratories, Ibaraki 300-1192, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Nahata
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: Yayoi
authors.initials: Y
authors.lastname: Saegusa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Iizuka
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000375:Aging / Q000502:physiology*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: 5-HT(2C)R; Aged; Food intake; Novelty; Rikkunshito