Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice.
The combination of depression and anorexia may influence morbidity and progressive physical disability in the elderly. Gender differences exist in hypothalamic-pituitary-adrenal axis activation following stress exposure. The objective of this study was to investigate gender differences in feeding behavior under novelty stress in aged mice. Food intake measurement, immunohistochemical assessment, and mRNA expression analysis were conducted to investigate the role of serotonin 2C receptor (5-HT(2C)R) and its relationship with ghrelin in stress-induced suppression of feeding behavior in aged mice. After exposure to novelty stress, a 21-fold increase in plasma corticosterone and remarkable suppression of food intake were observed in aged male mice. Furthermore, a 5-HT(2C)R agonist suppressed food intake in aged male mice. Novelty stress induced a 7-fold increase in 5-HT(2C)R and c-Fos co-expressing cells in the paraventricular nucleus of the hypothalamus in aged male mice but caused no change in aged female mice. Plasma acylated ghrelin levels decreased in stressed aged male mice and administration of the 5-HT(2C)R antagonist inhibited this decrease. The 5-HT(2C)R antagonist also reversed the suppression of food intake in estrogen receptor α agonist-treated aged male mice. Therefore, conspicuously suppressed feeding behavior in novelty stress-exposed aged male mice may be mediated by 5-HT(2C)R hypersensitivity, leading to hypoghrelinemia. The hypersensitivity may partly be due to estrogen receptor activation in aged male mice.
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Chihiro
C
Yamada
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Chiharu
C
Sadakane
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Miwa
M
Nahata
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Yayoi
Y
Saegusa
Pathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, N12 W6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
Koji
K
Nakagawa
Pathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, N12 W6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
Naoto
N
Okubo
Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Shunsuke
S
Ohnishi
Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Tomohisa
T
Hattori
Pathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, N12 W6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan; Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Electronic address: h_takeda@pharm.hokudai.ac.jp.
Hiroshi
H
Takeda
D000367:Age Factors; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000855:Anorexia; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D005260:Female; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D000077289:Letrozole; D008297:Male; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D012737:Sex Factors; D013315:Stress, Psychological; D014230:Triazoles / Q000494:pharmacology; D000097983:ERRalpha Estrogen-Related Receptor; D011422:Propionates
D000631:Aminopyridines; D047072:Aromatase Inhibitors; D003345:Corticosterone; D054439:Ghrelin; D007211:Indoles; D000077289:Letrozole; D009570:Nitriles; D010636:Phenols; D010879:Piperazines; D011719:Pyrazines; D011720:Pyrazoles; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D011960:Receptors, Estrogen; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D014230:Triazoles; D000097983:ERRalpha Estrogen-Related Receptor; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C000599853:5-hydroxytryptamine2C receptor, mouse; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C518685:CP-809,101; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
5-HT(2C)R; Aged; Food intake; Gender differences; Novelty stress; Rikkunshito