Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia

Alastair S. Garfield*, Luke K. Burke, Jill Shaw, Mark L. Evans, Lora K. Heisler

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)
4 Downloads (Pure)

Abstract

The central 5-hydroxytryptamine (5-HT; serotonin) system is well established as an important regulator of appetite and continues to remain a focus of obesity research. While much emphasis has focussed on the 5-HT2c receptor (5-HT2cR) in 5-HT's anorectic effect, pharmacological manipulation of the 5-HT6 receptor (5-HT6R) also reduces appetite and body weight and may be amenable to obesity treatment. However, the neurological circuits that underlie 5-HT6R-induced hypophagia remain to be identified. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation, here we mapped the neuroanatomical targets activated by an anorectic dose of the 5-HT6R antagonist SB-399885 throughout the brain. Furthermore, we quantified SB-399855 activated cells within brain appetitive nuclei, the hypothalamus, dorsal raphe nucleus (DRN) and nucleus of the solitary tract (NTS). Our results reveal that 5-HT6R antagonist-induced hypophagia is associated with significantly increased neuronal activation in two nuclei with an established role in the central control of appetite, the paraventricular nucleus of the hypothalamus (PVH) and the NTS. In contrast, no changes in FOS-IR were observed between treatment groups within other hypothalamic nuclei or DRN. The data presented here provide a first insight into the neural circuitry underlying 5-HT6R antagonist-induced appetite suppression and highlight the PVH and NTS in the coordination of 5-HT6R hypophagia. (C) 2014 The Authors. Published by Elsevier B.V.

Original languageEnglish
Pages (from-to)201-206
Number of pages6
JournalBehavioural Brain Research
Volume266
Early online date21 Feb 2014
DOIs
Publication statusPublished - 1 Jun 2014

Keywords

  • htr6
  • 5-HT6 receptor
  • SB-399885
  • food intake
  • hypothalamus
  • nucleus of the solitary tract
  • paraventricular nucleus
  • serotonin
  • neurons
  • obesity
  • brain
  • rat
  • fenfluramine
  • ligands

Cite this

Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia. / Garfield, Alastair S.; Burke, Luke K.; Shaw, Jill; Evans, Mark L.; Heisler, Lora K.

In: Behavioural Brain Research, Vol. 266, 01.06.2014, p. 201-206.

Research output: Contribution to journalArticle

Garfield, Alastair S. ; Burke, Luke K. ; Shaw, Jill ; Evans, Mark L. ; Heisler, Lora K. / Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia. In: Behavioural Brain Research. 2014 ; Vol. 266. pp. 201-206.
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AB - The central 5-hydroxytryptamine (5-HT; serotonin) system is well established as an important regulator of appetite and continues to remain a focus of obesity research. While much emphasis has focussed on the 5-HT2c receptor (5-HT2cR) in 5-HT's anorectic effect, pharmacological manipulation of the 5-HT6 receptor (5-HT6R) also reduces appetite and body weight and may be amenable to obesity treatment. However, the neurological circuits that underlie 5-HT6R-induced hypophagia remain to be identified. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation, here we mapped the neuroanatomical targets activated by an anorectic dose of the 5-HT6R antagonist SB-399885 throughout the brain. Furthermore, we quantified SB-399855 activated cells within brain appetitive nuclei, the hypothalamus, dorsal raphe nucleus (DRN) and nucleus of the solitary tract (NTS). Our results reveal that 5-HT6R antagonist-induced hypophagia is associated with significantly increased neuronal activation in two nuclei with an established role in the central control of appetite, the paraventricular nucleus of the hypothalamus (PVH) and the NTS. In contrast, no changes in FOS-IR were observed between treatment groups within other hypothalamic nuclei or DRN. The data presented here provide a first insight into the neural circuitry underlying 5-HT6R antagonist-induced appetite suppression and highlight the PVH and NTS in the coordination of 5-HT6R hypophagia. (C) 2014 The Authors. Published by Elsevier B.V.

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