Glucagon-like peptide-1 receptor agonist, liraglutide, reduces heroin self-administration and drug-induced reinstatement of heroin-seeking behaviour in rats
Open accessAbstract
Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP‐1 analogue, liraglutide (LIR), in reducing heroin addiction‐like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self‐administration, prevents escalation of heroin self‐administration and reduces drug‐induced reinstatement of heroin‐seeking behaviour in rats. A 1‐h pretreatment time, however, was too short to reduce cue‐induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR‐paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin‐naïve or heroin‐experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.
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For opioid dependence, exenatide reduced oxycodone intake, but not morphine intake, and liraglutide reduced heroin intake in rodents.
“For opioid dependence, exenatide reduced oxycodone intake, 114 but not morphine intake, 115 and liraglutide reduced heroin intake 116 in rodents, indicating some heterogeneity regarding the type of opioid drug.”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [116]
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- Authors
- Douton, J. E., Horvath, N., Mills‐Huffnagle, S., Nyland, J. E., Hajnal, A., & Grigson, P. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Pennsylvania State University (US)
- Department of Neural and Behavioral Sciences Penn State College of Medicine Hershey Pennsylvania USA
- Corresponding author
- Grigson, Patricia S.
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2021-11-21
- Volume
- 27
- Issue
- 2
- Pages
- e13117-e13117
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC10825889
- OpenAlex
- W3216846208
- Cited by
- 54
- References
- 43
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 9 · 2023: 6 · 2022: 7
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pennsylvania Department of Health (410007972)
- National Institute on Drug Abuse (DA009815, UG3 DA050325)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- liraglutide, GLP-1 receptor agonists, heroin self-administration, reinstatement of drug seeking, opioid use disorder, relapse, conditioned taste avoidance, dietary intake, body weight, overdose prevention
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Animals, Cues, Heroin, Heroin Dependence, Self Administration, Rats
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