Effect of ghrelin receptor antagonist on meal patterns in cholecystokinin type 1 receptor null mice

Jennifer Lee, Elizabeth Martin, Gabriel Paulino, Guillaume de Lartigue, Helen E Raybould

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Vagal afferent neurons (VAN) express the cholecystokinin (CCK) type 1 receptor (CCK1R) and, as predicted by the role of CCK in inducing satiation, CCK1R-/- mice ingest larger and longer meals. However, after a short fast, CCK1R-/- mice ingesting high fat (HF) diets initiate feeding earlier than wild-type mice. We hypothesized that the increased drive to eat in CCK1R-/- mice eating HF diet is mediated by ghrelin, a gut peptide that stimulates food intake. The decrease in time to first meal, and the increase in meal size and duration in CCK1R-/- compared to wild-type mice ingesting high fat (HF) diet were reversed by administration of GHSR1a antagonist D-(Lys3)-GHRP-6 (p<0.05). Administration of the GHSR1a antagonist significantly increased expression of the neuropeptide cocaine and amphetamine-regulated transcript (CART) in VAN of HF-fed CCK1R-/- but not wild-type mice. Administration of the GHSR1a antagonist decreased neuronal activity measured by immunoreactivity for fos protein in the nucleus of the solitary tract (NTS) and the arcuate nucleus of both HF-fed wild-type and CCK1R-/- mice. The data show that hyperphagia in CCK1R-/- mice ingesting HF diet is reversed by blockade of the ghrelin receptor, suggesting that in the absence of the CCK1R, there is an increased ghrelin-dependent drive to feed. The site of action of ghrelin receptors is unclear, but may involve an increase in expression of CART peptide in VAN in HF-fed CCK1R-/- mice.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalPhysiology and Behavior
Volume103
Issue number2
DOIs
StatePublished - May 3 2011

Keywords

  • C-fos
  • CCK
  • Ghrelin
  • Neuronal activation
  • Nodose ganglia

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Experimental and Cognitive Psychology

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