title: Ghrelin receptor (GHS-R1A) antagonism alters preference for ethanol and sucrose in a concentration-dependent manner in prairie voles.
abstract: Ghrelin receptor (GHS-R1A) activity has been implicated in reward for preferred foods and drugs; however, a recent study in our laboratory indicated that GHS-R1A antagonism reduces early (after only four exposures) preference for 20% ethanol, but not 10% sucrose in prairie voles, a genetically diverse high alcohol-consuming species. The purpose of the present study was to determine if these effects of GHS-R1A antagonism depend on the concentration of the rewarding solution being consumed. We first characterized preference for varying concentrations of ethanol and sucrose. Two bottle tests of each ethanol concentration versus water indicated that 10% and 20% ethanol are less preferred than 3% ethanol, and a follow-up direct comparison of 10% vs. 20% showed that 10% was preferred over 20%. Direct two-bottle comparisons of 2% vs. 5%, 2% vs. 10%, and 5% vs. 10% sucrose showed that 10% sucrose was most preferred, and 2% sucrose was least preferred. The effects of JMV 2959, a GHS-R1A antagonist, on preference for each concentration of ethanol and sucrose were then tested. In a between groups design prairie voles were given four two-hour drinking sessions in which animals had access to ethanol (3, 10, or 20%) versus water, or sucrose (2, 5, or 10%) versus water every other day. Saline habituation injections were given 30 min before the third drinking session. JMV 2959 (i.p.; 9 mg/kg), a GHS-R1A antagonist, or saline was administered 30 min before the fourth drinking session. JMV 2959 reduced preference for 20% ethanol and 2% sucrose, but had no significant effect on preference for the other ethanol and sucrose concentrations. These data identify constraints on the role of GHS-R1A in early preference for ethanol and sucrose, and the concentration-dependent effects suggest strong preference for a reward may limit the importance of GHS-R1A activity.
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA. Electronic address: j.stevenson@bucknell.edu.
authors.forename: J R
authors.initials: JR
authors.lastname: Stevenson
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Francomacaro
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Bohidar
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Young
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Pesarchick
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Buirkle
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: McMahon
authors.affiliation: Department of Psychology, Bucknell University, Lewisburg, PA 17837, USA; Program in Neuroscience, Bucknell University, Lewisburg, PA 17837, USA; Program in Animal Behavior, Bucknell University, Lewisburg, PA 17837, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: O'Bryan
mesh_terms: D000818:Animals; D003411:Arvicolinae; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D019422:Dietary Sucrose; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology; D060766:Drinking Water; D000431:Ethanol; D005260:Female; D005500:Follow-Up Studies; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D002491:Central Nervous System Agents; D019422:Dietary Sucrose; D060766:Drinking Water; 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
keywords: Ethanol; GHS-R1A antagonist; Ghrelin; Prairie vole; Reward; Sucrose