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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.

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Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark. Electronic address:
Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
Department of Experimental Medical Science, Appetite Regulation Unit, Faculty of Medicine, Lund University, Lund, Sweden.
Institute of Neuroscience and Physiology, Department of Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.


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.


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

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