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GLP-1 analog attenuates cocaine reward

Molecular Psychiatry volume 18, pages 961–962 (2013)Cite this article

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Glucagon-like peptide-1 (GLP-1) is released in response to food intake and acts through both peripheral and central mechanisms to regulate energy homeostasis and feeding behavior. Exendin-4 (Ex-4) is an analog of GLP-1 with a significantly longer half-life and greater potency,1 and is marketed synthetically as exenatide (Byetta and Bydureon) as a treatment for Type 2 diabetes mellitus. We show that administration of Ex-4 attenuates the rewarding effects of cocaine in mice, thus highlighting the therapeutic potential of GLP-1 receptor (GLP-1R) agonists for the treatment of psychostimulant addiction.

Emerging data suggest that hormones and peptides that have a role in feeding behavior, such as insulin, GLP-1, leptin, orexin and ghrelin, may also be involved in drug reward2, 3 and could thereby be targeted as therapies for the treatment of addiction. GLP1-Rs are expressed within the brain, including the ventral tegmental area (VTA) and the nucleus accumbens (NAc).4, 5 These brain regions are part of the mesolimbic reward circuit considered to have a major role in the rewarding properties of drugs, including cocaine.6 Activation of mesolimbic GLP-1Rs decreases the intake of highly palatable foods, suggesting that GLP-1R activation contributes to the hedonic components of food intake.4 Drug reward and feeding behavior utilize overlapping brain circuitry and mechanisms, thus we hypothesized that the GLP-1R agonist Ex-4 would reduce the rewarding effects of cocaine.

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Author notes

  1. A Galli and G D Stanwood: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

    D L Graham & G D Stanwood

  2. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    K Erreger & A Galli

  3. Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    K Erreger, A Galli & G D Stanwood

Authors
  1. D L Graham
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  2. K Erreger
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  3. A Galli
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  4. G D Stanwood
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Correspondence to G D Stanwood.

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Graham, D., Erreger, K., Galli, A. et al. GLP-1 analog attenuates cocaine reward. Mol Psychiatry 18, 961–962 (2013). https://doi.org/10.1038/mp.2012.141

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