Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT 2C receptor inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors

Katsunori Nonogaki, Kana Nozue, Yukiko Takahashi, Nobuyuki Yamashita, Shuichi Hiraoka, Hiroaki Kumano, Tomifusa Kuboki, Yohsitomo Oka

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the appetite-suppressing effects of 5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084 alone has no effect. The appetite-suppressing effects were attenuated in the presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist. Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted appetite-suppressing effects and significantly increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression and decreased hypothalamic orexin gene expression. These results suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors, and that 5-HT1C receptors up-regulate hypothalamic POMC and CART gene expression and down-regulate hypothalamic orexin gene expression in mice.

Original languageEnglish
Pages (from-to)675-681
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume10
Issue number5
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • 5-HT receptor
  • 5-HT receptor
  • Appetite
  • POMC
  • SSRI

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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