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Delayed satiety-like actions and altered feeding microstructure by a selective type 2 corticotropin-releasing factor agonist in rats: Intra-hypothalamic urocortin 3 administration reduces food intake by prolonging the post-meal interval

Academic Article
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Overview

authors

  • Fekete, E. M.
  • Inoue, K.
  • Zhao, Y.
  • Rivier, J. E.
  • Vale, W. W.
  • Szucs, A.
  • Koob, George
  • Zorrilla, Eric

publication date

  • May 2007

journal

  • Neuropsychopharmacology  Journal

abstract

  • Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of 'type 2' urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n=176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF(2) receptors. LV Ucn 3 suppressed ingestion during the third-fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin(2)-B, a selective CRF(2) antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57-73%) and duration of ingestion (32-68%) during the third-fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF(2) control of food intake.

subject areas

  • Amygdala
  • Animals
  • Appetite Regulation
  • Corticotropin-Releasing Hormone
  • Feeding Behavior
  • Hypothalamus
  • Injections, Intraventricular
  • Male
  • Neural Pathways
  • Paraventricular Hypothalamic Nucleus
  • Peptide Fragments
  • Rats
  • Rats, Wistar
  • Reaction Time
  • Receptors, Corticotropin-Releasing Hormone
  • Satiety Response
  • Time Factors
  • Urocortins
  • Ventromedial Hypothalamic Nucleus
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Research

keywords

  • corticotropin-releasing factor or corticotropin releasing hormone
  • food intake or feeding
  • meal pattern or microstructure
  • medial amygdala
  • urocortin 1 or urocortin 3
  • ventromedial hypothalamic nucleus or paraventricular nucleus of the hypothalamus
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Identity

PubMed Central ID

  • PMC2748839

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/sj.npp.1301214

PubMed ID

  • 17019404
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Additional Document Info

start page

  • 1052

end page

  • 1068

volume

  • 32

issue

  • 5

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