Requirement of central ghrelin signaling for alcohol reward.
The stomach-derived hormone ghrelin interacts with key CNS circuits regulating energy balance and body weight. Here we provide evidence that the central ghrelin signaling system is required for alcohol reward. Central ghrelin administration (to brain ventricles or to tegmental areas involved in reward) increased alcohol intake in a 2-bottle (alcohol/water) free choice limited access paradigm in mice. By contrast, central or peripheral administration of ghrelin receptor (GHS-R1A) antagonists suppressed alcohol intake in this model. Alcohol-induced locomotor stimulation, accumbal dopamine release and conditioned place preference were abolished in models of suppressed central ghrelin signaling: GHS-R1A knockout mice and mice treated with 2 different GHS-R1A antagonists. Thus, central ghrelin signaling, via GHS-R1A, not only stimulates the reward system, but is also required for stimulation of that system by alcohol. Our data suggest that central ghrelin signaling constitutes a potential target for treatment of alcohol-related disorders.
Jerlhag
Elisabet
E
Section for Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, SE-405 30 Gothenburg, Sweden. elisabet.jerlhag@pharm.gu.se
Egecioglu
Emil
E
Landgren
Sara
S
Salomé
Nicolas
N
Heilig
Markus
M
Moechars
Diederik
D
Datta
Rakesh
R
Perrissoud
Daniel
D
Dickson
Suzanne L
SL
Engel
Jörgen A
JA
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008957:Models, Genetic; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects
D054439:Ghrelin; D054440:Receptors, Ghrelin; D000431:Ethanol; D004298:Dopamine