Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.
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.
Verhagen
Linda A W
LA
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, Utrecht, The Netherlands.
Egecioglu
Emil
E
Luijendijk
Mieneke C M
MC
Hillebrand
Jacquelien J G
JJ
Adan
Roger A H
RA
Dickson
Suzanne L
SL
D000704:Analysis of Variance; D000818:Animals; D000856:Anorexia Nervosa / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000235:genetics / Q000523:psychology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D054439:Ghrelin / Q000097:blood*; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000172:deficiency; D012420:Running; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D054439:Ghrelin; D054440:Receptors, Ghrelin