Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity

Eur Neuropsychopharmacol. 2011 May;21(5):384-92. doi: 10.1016/j.euroneuro.2010.06.005.

Abstract

Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anorexia Nervosa / drug therapy
  • Anorexia Nervosa / genetics
  • Anorexia Nervosa / metabolism*
  • Anorexia Nervosa / pathology
  • Body Weight / drug effects
  • Body Weight / genetics
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Eating / genetics
  • Eating / psychology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Food Deprivation / physiology
  • Ghrelin / blood*
  • Hyperkinesis / genetics
  • Hyperkinesis / metabolism
  • Injections, Intraventricular / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Rats
  • Rats, Wistar
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Ghrelin / deficiency
  • Running
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Enzyme Inhibitors
  • Ghrelin
  • Receptors, Ghrelin