Document Detail

The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents.
MedLine Citation:
PMID:  23219472     Owner:  NLM     Status:  MEDLINE    
Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.
Emil Egecioglu; Pia Steensland; Ida Fredriksson; Kristin Feltmann; Jörgen A Engel; Elisabet Jerlhag
Publication Detail:
Type:  Journal Article     Date:  2012-12-07
Journal Detail:
Title:  Psychoneuroendocrinology     Volume:  38     ISSN:  1873-3360     ISO Abbreviation:  Psychoneuroendocrinology     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2014-01-31     Revised Date:  2014-03-25    
Medline Journal Info:
Nlm Unique ID:  7612148     Medline TA:  Psychoneuroendocrinology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1259-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Choice Behavior / drug effects*
Conditioning (Psychology) / drug effects
Conditioning, Operant / drug effects
Dopamine / metabolism
Dose-Response Relationship, Drug
Drug-Seeking Behavior / drug effects*,  physiology*
Ethanol / administration & dosage,  antagonists & inhibitors*,  pharmacology
Glucagon-Like Peptide 1 / analogs & derivatives,  physiology*
Motor Activity / drug effects
Nucleus Accumbens / drug effects,  metabolism
Peptides / pharmacology*
Self Administration
Venoms / pharmacology*
Reg. No./Substance:
0/Peptides; 0/Venoms; 3K9958V90M/Ethanol; 89750-14-1/Glucagon-Like Peptide 1; 9P1872D4OL/exenatide; VTD58H1Z2X/Dopamine

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