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

Authors :
Anders Fink-Jensen
Gitta Wörtwein
Elisabet Jerlhag
Pia Weikop
Morgane Thomsen
Ditte Dencker
Anna Molander
Emil Egecioglu
Source :
Pharmacology Biochemistry and Behavior. 160:14-20
Publication Year :
2017
Publisher :
Elsevier BV, 2017.

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 in the home cage for 37days. Then, alcohol bottles were removed and Exendin-4 (1.5μg/kg/day) or saline was administered subcutaneously for 8days 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.

Details

ISSN :
00913057
Volume :
160
Database :
OpenAIRE
Journal :
Pharmacology Biochemistry and Behavior
Accession number :
edsair.doi.dedup.....8e5c64cc223f97f954ba7b2823b3ce29
Full Text :
https://doi.org/10.1016/j.pbb.2017.07.014