title: Urocortin1-induced anorexia is regulated by activation of the serotonin 2C receptor in the brain.
abstract: This study was conducted to determine the mechanisms by which serotonin (5-hydroxytryptamine, 5-HT) receptors are involved in the suppression of food intake in a rat stress model and to observe the degree of activation in the areas of the brain involved in feeding. In the stress model, male Sprague-Dawley rats (8 weeks old) were given intracerebroventricular injections of urocortin (UCN) 1. To determine the role of the 5-HT2c receptor (5-HT2cR) in the decreased food intake in UCN1-treated rats, specific 5-HT2cR or 5-HT2b receptor (5-HT2bR) antagonists were administered. Food intake was markedly reduced in UCN1-injected rats compared with phosphate buffered saline treated control rats. Intraperitoneal administration of a 5-HT2cR antagonist, but not a 5-HT2bR antagonist, significantly inhibited the decreased food intake. To assess the involvement of neural activation, we tracked the expression of c-fos mRNA as a neuronal activation marker. Expression of the c-fos mRNA in the arcuate nucleus, ventromedial hypothalamic nucleus (VMH) and rostral ventrolateral medulla (RVLM) in UNC1-injected rats showed significantly higher expression than in the PBS-injected rats. Increased c-fos mRNA was also observed in the paraventricular nucleus (PVN), the nucleus of the solitary tract (NTS), and the amygdala (AMG) after injection of UCN1. Increased 5-HT2cR protein expression was also observed in several areas. However, increased coexpression of 5-HT2cR and c-fos was observed in the PVN, VMH, NTS, RVLM and AMG. Whereas, pro-opiomelanocortin mRNA expression was not changed. In an UNC1-induced stress model, 5-HT2cR expression and activation was found in brain areas involved in feeding control.
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, Kawagoe, Saitama, Japan; Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Department of Laboratory Sciences, Gunma University School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Kiyoshige
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, Kawagoe, Saitama, Japan; Central Research Laboratories, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Shoki
authors.initials: S
authors.lastname: Ro
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, Kawagoe, Saitama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Ochiai
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Iizuka
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Gastroenterology and Hepatology, Saitama Medical University, Kawagoe, Saitama, Japan. Electronic address: kjyakabi@saitama-med.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Yakabi
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism*; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D054832:Urocortins
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D016760:Proto-Oncogene Proteins c-fos; D011804:Quinolines; D044405:Receptor, Serotonin, 5-HT2C; C118948:SB 215505; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D054832:Urocortins; D011333:Pro-Opiomelanocortin
keywords: 5-HT2cR; Activation; Anorexia; CRF neuron; Food intake; Stress