Advanced

The glucagon-like peptide 1 receptor agonist Exendin-4 decreases relapse-like drinking in socially housed mice

Thomsen, Morgane; Dencker, Ditte; Wörtwein, Gitta; Weikop, Pia; Egecioglu, Emil LU ; Jerlhag, Elisabet; Fink-Jensen, Anders and Molander, Anna (2017) In Pharmacology Biochemistry and Behavior 160. p.14-20
Abstract

Glucagon-like peptide-1 (GLP-1) is a gut peptide that regulates food intake and glucose metabolism. GLP-1 is also produced and released in the brain, and GLP-1 receptors are expressed in brain regions important for alcohol and drug reward, and for the development of addiction. GLP-1 receptor agonists can decrease alcohol intake acutely in rodents. However, alcohol use disorder is a chronic condition that requires treatments to be effective in promoting abstinence from excessive alcohol consumption over time. Here, we assessed the effect of daily treatment with the GLP-1 receptor agonist Exendin-4 in an assay of relapse-like drinking in socially housed mice. Male C57BL/6NTac mice were allowed continuous access to alcohol without tastant... (More)

Glucagon-like peptide-1 (GLP-1) is a gut peptide that regulates food intake and glucose metabolism. GLP-1 is also produced and released in the brain, and GLP-1 receptors are expressed in brain regions important for alcohol and drug reward, and for the development of addiction. GLP-1 receptor agonists can decrease alcohol intake acutely in rodents. However, alcohol use disorder is a chronic condition that requires treatments to be effective in promoting abstinence from excessive alcohol consumption over time. Here, we assessed the effect of daily treatment with the GLP-1 receptor agonist Exendin-4 in an assay of relapse-like drinking in socially housed mice. Male C57BL/6NTac mice were allowed continuous access to alcohol without tastant in the home cage for 37 days. Then, alcohol bottles were removed and Exendin-4 (1.5 μg/kg/day) or saline was administered subcutaneously for 8 days during alcohol deprivation. Treatment continued for 8 additional days after reintroducing access to alcohol. A high-precision automated fluid consumption system was used to monitor intake of alcohol and water, drinking kinetics, and locomotor activity. Exendin-4 prevented the deprivation-induced increase in alcohol intake observed in control mice, without significantly affecting total fluid intake, body weight, or locomotor activity. The reduced alcohol intake was caused by a protracted latency to the first drink of alcohol and a reduced number of drinking bouts, while bout size and duration were not affected. The effect was maintained undiminished throughout the treatment period. These findings support the possible use of GLP-1 receptor agonists in the treatment of alcohol use disorder.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alcohol deprivation, Alcoholism, Ethanol, Exenatide, Group-housed, Incretin hormones
in
Pharmacology Biochemistry and Behavior
volume
160
pages
7 pages
publisher
Elsevier
external identifiers
  • scopus:85026833408
  • wos:000412617800002
ISSN
0091-3057
DOI
10.1016/j.pbb.2017.07.014
language
English
LU publication?
yes
id
3241fa86-be58-4050-ad43-2e32424e98cd
date added to LUP
2017-08-29 11:15:42
date last changed
2018-01-16 13:23:44
@article{3241fa86-be58-4050-ad43-2e32424e98cd,
  abstract     = {<p>Glucagon-like peptide-1 (GLP-1) is a gut peptide that regulates food intake and glucose metabolism. GLP-1 is also produced and released in the brain, and GLP-1 receptors are expressed in brain regions important for alcohol and drug reward, and for the development of addiction. GLP-1 receptor agonists can decrease alcohol intake acutely in rodents. However, alcohol use disorder is a chronic condition that requires treatments to be effective in promoting abstinence from excessive alcohol consumption over time. Here, we assessed the effect of daily treatment with the GLP-1 receptor agonist Exendin-4 in an assay of relapse-like drinking in socially housed mice. Male C57BL/6NTac mice were allowed continuous access to alcohol without tastant in the home cage for 37 days. Then, alcohol bottles were removed and Exendin-4 (1.5 μg/kg/day) or saline was administered subcutaneously for 8 days during alcohol deprivation. Treatment continued for 8 additional days after reintroducing access to alcohol. A high-precision automated fluid consumption system was used to monitor intake of alcohol and water, drinking kinetics, and locomotor activity. Exendin-4 prevented the deprivation-induced increase in alcohol intake observed in control mice, without significantly affecting total fluid intake, body weight, or locomotor activity. The reduced alcohol intake was caused by a protracted latency to the first drink of alcohol and a reduced number of drinking bouts, while bout size and duration were not affected. The effect was maintained undiminished throughout the treatment period. These findings support the possible use of GLP-1 receptor agonists in the treatment of alcohol use disorder.</p>},
  author       = {Thomsen, Morgane and Dencker, Ditte and Wörtwein, Gitta and Weikop, Pia and Egecioglu, Emil and Jerlhag, Elisabet and Fink-Jensen, Anders and Molander, Anna},
  issn         = {0091-3057},
  keyword      = {Alcohol deprivation,Alcoholism,Ethanol,Exenatide,Group-housed,Incretin hormones},
  language     = {eng},
  month        = {09},
  pages        = {14--20},
  publisher    = {Elsevier},
  series       = {Pharmacology Biochemistry and Behavior},
  title        = {The glucagon-like peptide 1 receptor agonist Exendin-4 decreases relapse-like drinking in socially housed mice},
  url          = {http://dx.doi.org/10.1016/j.pbb.2017.07.014},
  volume       = {160},
  year         = {2017},
}