Requirement of central ghrelin signaling for alcohol reward

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 27; pp. 11318 - 11323
• Main Authors: Jerlhag, Elisabet, Egecioglu, Emil, Landgren, Sara, Salomé, Nicolas, Heilig, Markus, Moechars, Diederik, Datta, Rakesh, Perrissoud, Daniel, Dickson, Suzanne L, Engel, Jörgen A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07.07.2009; National Acad Sciences
• Subjects: administration & dosage; Alcohol drinking; Alcohol use; Alcoholic beverages; Alcohols; Animals; Antagonist drugs; antagonists; antagonists & inhibitors; Biological; Biological Sciences; Body weight; Central Nervous System; Central Nervous System - drug effects; Central Nervous System - metabolism; Classical; Conditioning; Conditioning, Classical - drug effects; Dopamine; Dopamine - metabolism; Drug design; drug effects; Energy balance; Ethanol; Ethanol - administration & dosage; Food intake; Fysiologi och anatomi; Genetic; Ghrelin; Ghrelin - administration & dosage; Ghrelin - metabolism; Ghrelin - pharmacology; ghrelin receptors; Hormones; Inbred C57BL; Injections; Injections, Intraperitoneal; Injections, Intraventricular; Intraperitoneal; Intraventricular; Knockout mice; knockout mutants; Medical treatment; metabolism; Mice; Mice, Inbred C57BL; Models, Biological; Models, Genetic; Motor Activity; Motor Activity - drug effects; Nucleus Accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Pharmacology; Physiology and Anatomy; Receptors; Receptors, Ghrelin - antagonists & inhibitors; Reward; Rodents; Signal Transduction; Signal Transduction - drug effects; Vehicles; Ventral Tegmental Area; Ventral Tegmental Area - drug effects
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0812809106

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.