Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice

Yamada, Chihiro; Sadakane, Chiharu; Nahata, Miwa; Saegusa, Yayoi; Nakagawa, Koji; Okubo, Naoto; Ohnishi, Shunsuke; Hattori, Tomohisa; Takeda, Hiroshi

doi:10.1016/j.psyneuen.2015.02.006

Cited by 15 publications

(44 citation statements)

References 46 publications

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“…The administered dose of RKT is approximately equivalent to a typical clinical dose when converted based on body surface area (as recommended by the FDA) and this dose has previously been reported to show ameliorative effects in a mouse model of anorexia13144041. Cumulative food intake was determined at 1, 3 and 6 h after stress exposure.…”

Section: Methodsmentioning

confidence: 99%

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Mogami

Sadakane

Nahata

et al. 2016

Sci Rep

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Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities.

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Section: Methodsmentioning

confidence: 99%

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Mogami

Sadakane

Nahata

et al. 2016

Sci Rep

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“…Ghrelin, a hormone produced in the peripheral organs and central nervous system, is known to be involved in the regulation of appetite, gastrointestinal motility, and growth hormone release. Recently, the abnormal kinetics of ghrelin due to stress loading have been reported [ 1 – 3 , 9 , 10 ]. Intracerebroventricular administration of CRF or exposure to psychological stress suppresses food intake in association with decreases in peripheral ghrelin levels during fasting [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the abnormal kinetics of ghrelin due to stress loading have been reported [ 1 – 3 , 9 , 10 ]. Intracerebroventricular administration of CRF or exposure to psychological stress suppresses food intake in association with decreases in peripheral ghrelin levels during fasting [ 1 , 3 ]. In ghrelin deficienct conditions, the administration of exogenous acylated ghrelin or the endogenous ghrelin enhancer rikkunshito clearly recovers the effect of stress-induced hypophagia [ 1 – 4 , 6 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Aging and Gender Differences on Feeding Behavior and Ghrelin-Related Factors during Social Isolation in Mice

et al. 2015

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Psychological stress due to social isolation is known to cause abnormal feeding behaviors, but the influences of gender and aging on subchronic stress-induced changes in feeding behaviors are unknown. Thus, we examined the changes in body weight, food intake, and orexigenic ghrelin-related factors during 2 weeks of isolation stress in young and aged mice. Food intake increased significantly in young mice in the isolation group compared with the group-housed control throughout the experimental period. This isolation-induced increase in food intake was not observed in aged mice. In young mice, there were no significant differences in body weight between the isolated group and group-housed control up to 2 weeks. However, aged male mice exhibited significant weight loss at 2 weeks and a similar tendency was observed in aged female mice. Young male mice, but not female mice, had significantly increased (2.2-fold) plasma acylated ghrelin levels after 1 week of isolation compared with the group-housed control. A significant but lower increase (1.3-fold) was also observed in aged male mice. Hypothalamic preproghrelin gene expression decreased significantly with isolation in young male mice, whereas it increased significantly in female mice. The expression levels of NPY and AGRP in the hypothalamus, which are transmitted by elevated peripheral ghrelin signals, increased significantly in isolated young male mice, whereas the AGRP expression levels decreased significantly in young female mice. Isolation caused no significant differences in the expression levels of these genes in aged mice. In isolation, young female mice exhibited markedly increased dark- and light-phase locomotor activities compared with male mice, whereas male and female aged mice exhibited no obvious increases in activity immediately after the dark phase started. We conclude that the gender-specific homeostatic regulatory mechanisms required to maintain body weight operated during subchronic psychological stress in young mice but not in aged mice.

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“…RKT (0.5 g/kg) or vehicle (distilled water, 4 ml/kg) was given daily by orogastric gavage for 7 days, and on day 8, at 6 h and 1 h before the abdominal surgery that took place at 1–2 h before the dark phase. The last RKT treatment before surgery was to maintain the effect based on previous studies showing that RKT administered at 1 h before novelty stress in mice improves feeding [ 26 – 28 ]. Non-surgery controls remained in their home cages.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, we demonstrated that RKT blocked L-dopa-inhibited gastric emptying in rats [ 25 ]. RKT can also restore novelty stress-induced reduction of food intake in mice [ 26 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito

et al. 2015

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Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6–7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1–2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92–86% suppression of food intake at 2–24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.

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Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice

Cited by 15 publications

References 46 publications

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Influence of Aging and Gender Differences on Feeding Behavior and Ghrelin-Related Factors during Social Isolation in Mice

Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito

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