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Serotonin 2C receptor antagonism ameliorates novelty-induced hypophagia in aged mice

Miwa Nahata1, Shuichi Muto, Koji Nakagawa

  • 1Tsumura & Co., Tsumura Research Laboratories, Ibaraki 300-1192, Japan.

Psychoneuroendocrinology
|April 16, 2013
PubMed

Insights

Aged mice show reduced food intake and increased stress when exposed to novel environments. Enhanced serotonin (5-hydroxytryptamine, 5-HT) 2C receptor signaling in the hypothalamus contributes to this novelty-induced hypophagia.

Area of Science:

  • Neuroscience
  • Gerontology
  • Pharmacology

Background:

  • Aging is associated with altered responses to environmental stimuli.
  • Novelty-induced hypophagia, a decrease in food intake due to new environments, is exacerbated in aged individuals.
  • Serotonin (5-hydroxytryptamine, 5-HT) 2C receptor (5-HT2CR) signaling is implicated in appetite regulation and stress responses.

Purpose of the Study:

  • To investigate the role of 5-HT2CR signaling in novelty-induced hypophagia in aged mice.
  • To compare the effects of novel environments on feeding behavior and stress hormones in young and aged mice.
  • To explore potential therapeutic interventions targeting 5-HT2CR.

Main Methods:

  • Male C57BL/6J mice (young and aged) were exposed to a novel environment.
  • Feeding behavior, corticosterone levels, and hypothalamic gene expression (CRF, CRF1R, POMC) were measured.
  • The effects of 5-HT2CR antagonists (SB242084, rikkunshito) were evaluated.

Main Results:

  • Aged mice exhibited suppressed food intake and elevated corticosterone secretion in novel environments compared to young mice.
  • Hypothalamic CRF and pituitary CRF1R/POMC mRNA expression increased in aged mice exposed to novelty.
  • 5-HT2CR antagonist administration attenuated hypophagia and reduced stress hormone levels in aged mice.
  • 5-HT2CR mRNA expression in the paraventricular nucleus was significantly upregulated in aged mice upon environmental change.

Conclusions:

  • Up-regulated hypothalamic 5-HT2CR function contributes to novelty-induced hypophagia in aged mice.
  • Enhanced 5-HT2CR signaling and subsequent corticotropin-releasing factor (CRF) neuron activation are involved in this phenomenon.
  • 5-HT2CR antagonists represent a potential therapeutic strategy for conditions like depression associated with altered appetite and stress responses.
Keywords:
5-HT(2C)RAgedFood intakeNoveltyRikkunshito

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