GLP-1 Influences Food and Drug Reward
Open accessAbstract
Natural rewards, including food, water, sleep and social interactions, are required to sustain life. The neural substrates that regulate the reinforcing effects of these behaviors are also the same neurobiological mechanisms mediating mood, motivation and the rewarding effects of pharmacological stimuli. That the neuropeptide glucagon-like peptide-1 (GLP-1) is under investigation for both the homeostatic and hedonic controls of feeding is not surprising or novel. However, if the neural substrates that underline food reward are shared with other reward-related behaviors generally, then future research should investigate and embrace the likelihood that endogenous and exogenous GLP-1 receptor activation may influence multiple reward-related behaviors. Indeed, studies of the neurobiological mechanisms underlying motivated feeding behavior have informed much of the basic research investigating neural substrates of drug addiction. An emerging literature demonstrates a role for the GLP-1 system in modulating maladaptive reward behaviors, including drug and alcohol consumption. Thus, if GLP-1-based pharmacotherapies are to be used to treat drug addiction and other diseases associated with maladaptive reward behaviors (e.g. obesity and eating disorders), the neuroscience field must conduct systematic, mechanistic neuropharmacological and behavioral studies of each GLP-1 receptor-expressing nucleus within the brain. It is possible that behavioral selectivity may result from these studies, which could inform future approaches to targeting GLP-1R signaling in discrete brain nuclei to treat motivated behaviors. Equally as likely, non-selective effects on natural reward and maladaptive reward behaviors may be observed for GLP-1-based pharmacotherapies. In this case, a better understanding of the effects of increased central GLP-1R activation on motivated behaviors will aid in clinical approaches toward treating aberrant feeding behaviors and/or drug dependence.
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Activation of central GLP-1 receptors attenuates dopamine-mediated reward pathways, reducing the incentive salience of food.
“Activation of central GLP-1 receptors attenuates these dopamine-mediated reward pathways, reducing the incentive salience of food [59].”
From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [59]
The “Central actions of GLP-1 on food and drug rewards” section (page unavailable) reports that GLP-1 receptor activation in mesolimbic nuclei reduces palatable-food intake and may reduce the motivational incentive of rewarding food. It does not establish attenuation of dopamine-mediated pathways as the mechanism, and it frames the motivational effect as a possibility rather than a settled result. (LLM, conf=0.86)
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“Activation of central GLP-1 receptors attenuates these dopamine-mediated reward pathways, reducing the incentive salience of food [59].”
- Authors
- Hayes, M. R., & Schmidt, H. D.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hayes, Matthew R
- Schmidt, Heath D
- Venue
- Current Opinion in Behavioral Sciences
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 9
- Pages
- 66-70
- ISSN
- 2352-1546 (ISSN-L)
- PMC
- PMC4822543
- OpenAlex
- W2261355898
- Cited by
- 108
- References
- 44
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 7 · 2023: 10 · 2022: 4 · 2021: 14 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 4 · 2016: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Behavioral Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01-DA037897, R01-DK096139)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, food reward, drug reward, drug addiction, natural reward, obesity, eating disorders, brain nuclei, neuropharmacology
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