title: Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats.
abstract: The mechanisms involved in alcohol use disorders are complex. It has been shown that ghrelin is an important signal for the control of body weight homeostasis, preferably by interacting with hypothalamic circuits, as well as for drug reward by activating the mesolimbic dopamine system. The ghrelin receptor (GHS-R1A) has been shown to be required for alcohol-induced reward. Additionally, ghrelin increases and GHR-R1A antagonists reduce moderate alcohol consumption in mice, and a single nucleotide polymorphism in the GHS-R1A gene has been associated with high alcohol consumption in humans. However, the role of central ghrelin signaling in high alcohol consumption is not known. Therefore, the role of GHS-R1A in operant self-administration of alcohol in rats as well as for high alcohol consumption in Long-Evans rats and in alcohol preferring [Alko alcohol (AA)] rats was studied here. In the present study, the GHS-R1A antagonist, JMV2959, was found to reduce the operant self-administration of alcohol in rats and to decrease high alcohol intake in Long-Evans rats as well as in AA rats. These results suggest that the ghrelin receptor signaling system, specifically GHS-R1A, is required for operant self-administration of alcohol and for high alcohol intake in rats. Therefore, the GHS-R1A may be a therapeutic target for treatment of addictive behaviors, such as alcohol dependence.
authors.affiliation: Section for Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Landgren
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simms
authors.forename: Petri
authors.initials: P
authors.lastname: Hyytiä
authors.forename: Jörgen A
authors.initials: JA
authors.lastname: Engel
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
authors.forename: Elisabet
authors.initials: E
authors.lastname: Jerlhag
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors*; D012646:Self Administration / Q000706:statistics & numerical data; D015398:Signal Transduction / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D054440:Receptors, Ghrelin; D014230:Triazoles; D000431:Ethanol; D005998:Glycine