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Pharmacol Biochem Behav. 2017 Sep;160:14-20. doi: 10.1016/j.pbb.2017.07.014. Epub 2017 Aug 1.

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

Author information

1
Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark. Electronic address: morgane.marie.thomsen@regionh.dk.
2
Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
3
Department of Experimental Medical Science, Appetite Regulation Unit, Faculty of Medicine, Lund University, Lund, Sweden.
4
Institute of Neuroscience and Physiology, Department of Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

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.

KEYWORDS:

Alcohol deprivation; Alcoholism; Ethanol; Exenatide; Group-housed; Incretin hormones

PMID:
28778739
DOI:
10.1016/j.pbb.2017.07.014
[Indexed for MEDLINE]

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