Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence

Juan L. Gomez, Christopher Cunningham, Deborah (Deb) Finn, Emily A. Young, Lily K. Helpenstell, Lindsey M. Schuette, Tara L. Fidler, Therese A. Kosten, Andrey Ryabinin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.

Original languageEnglish (US)
Pages (from-to)182-193
Number of pages12
JournalNeuropharmacology
Volume97
DOIs
StatePublished - Jun 27 2015

Fingerprint

Ghrelin
Ghrelin Receptor
Alcohol Drinking
Alcoholism
Ethanol
Self Administration
Inbred C57BL Mouse
Drinking
Drug-Seeking Behavior
Compulsive Behavior
Hunger
Street Drugs
Reward
Pharmaceutical Preparations
Growth Hormone
Sucrose
Wistar Rats
Rodentia
Homeostasis
Alcohols

Keywords

  • Ethanol vapor
  • Ghrelin
  • Intragastric infusions
  • Self-administration
  • Two-bottle choice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence. / Gomez, Juan L.; Cunningham, Christopher; Finn, Deborah (Deb); Young, Emily A.; Helpenstell, Lily K.; Schuette, Lindsey M.; Fidler, Tara L.; Kosten, Therese A.; Ryabinin, Andrey.

In: Neuropharmacology, Vol. 97, 27.06.2015, p. 182-193.

Research output: Contribution to journalArticle

Gomez, Juan L. ; Cunningham, Christopher ; Finn, Deborah (Deb) ; Young, Emily A. ; Helpenstell, Lily K. ; Schuette, Lindsey M. ; Fidler, Tara L. ; Kosten, Therese A. ; Ryabinin, Andrey. / Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence. In: Neuropharmacology. 2015 ; Vol. 97. pp. 182-193.
@article{7201b99d8b56430182a682787029d084,
title = "Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence",
abstract = "An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.",
keywords = "Ethanol vapor, Ghrelin, Intragastric infusions, Self-administration, Two-bottle choice",
author = "Gomez, {Juan L.} and Christopher Cunningham and Finn, {Deborah (Deb)} and Young, {Emily A.} and Helpenstell, {Lily K.} and Schuette, {Lindsey M.} and Fidler, {Tara L.} and Kosten, {Therese A.} and Andrey Ryabinin",
year = "2015",
month = "6",
day = "27",
doi = "10.1016/j.neuropharm.2015.05.026",
language = "English (US)",
volume = "97",
pages = "182--193",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence

AU - Gomez, Juan L.

AU - Cunningham, Christopher

AU - Finn, Deborah (Deb)

AU - Young, Emily A.

AU - Helpenstell, Lily K.

AU - Schuette, Lindsey M.

AU - Fidler, Tara L.

AU - Kosten, Therese A.

AU - Ryabinin, Andrey

PY - 2015/6/27

Y1 - 2015/6/27

N2 - An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.

AB - An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.

KW - Ethanol vapor

KW - Ghrelin

KW - Intragastric infusions

KW - Self-administration

KW - Two-bottle choice

UR - http://www.scopus.com/inward/record.url?scp=84933046717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933046717&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2015.05.026

DO - 10.1016/j.neuropharm.2015.05.026

M3 - Article

C2 - 26051399

AN - SCOPUS:84933046717

VL - 97

SP - 182

EP - 193

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -