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

Received 22 February 2010; received in revised form 19 May 2010; accepted 12 June 2010. published online 12 July 2010.
Corrected Proof

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.

Keywords: Ghrelin, GHS-R1A antagonist, Activity-based anorexia, Food anticipatory activity, Running wheel activity, JMV2959

a Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands

b Institute of Neuroscience and Physiology, Department of Physiology/Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

c Rintveld Centre for Eating Disorders, Altrecht Mental Health Institute, Zeist, The Netherlands

d ETH Zurich, Institute of Animal Sciences, Physiology and Behaviour, Schwerzenbach, Switzerland

Corresponding author. Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Tel.: +31 88 756 8517; fax: +31 88 756 9032.

1 Present address: Institute for Genetics, Department of Mouse Genetics and Metabolism, University of Cologne, Cologne, Germany.

2 These authors contributed equally to this work.

3 These are both senior authors.

PII: S0924-977X(10)00118-5

doi:10.1016/j.euroneuro.2010.06.005