Hyperphagic effects of brainstem ghrelin administration

Diabetes. 2003 Sep;52(9):2260-5. doi: 10.2337/diabetes.52.9.2260.

Abstract

The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response approximately 3 h after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Stem / drug effects*
  • Brain Stem / physiology*
  • Eating / drug effects
  • Eating / physiology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Fourth Ventricle
  • Ghrelin
  • Hyperphagia / physiopathology*
  • Injections, Intraventricular
  • Male
  • Microinjections
  • Peptide Hormones / pharmacology*
  • Peptide Hormones / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Third Ventricle

Substances

  • Ghrelin
  • Peptide Hormones