ArticleNeuropharmacology2021
A novel dual agonist of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors attenuates fentanyl taking and seeking in male rats.
Article in Neuropharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Glucagon-like peptide-1 receptor agonists for the treatment of opioid use disorders: a systematic review.Acta neuropsychiatrica · 2025Pooled it
- Acute glucagon-like peptide-1 receptor agonist, semaglutide, attenuates cue-, drug-, and stress-induced fentanyl seeking in male Sprague-Dawley rats.Behavioural pharmacology · 2026Article
- Review
- A rapid review of the effects of GLP-1 receptor agonists on opioid and stimulant use-related outcomes.Drug and alcohol dependence reports · 2026Review
- Glucagon-like peptide-1 receptor agonist, semaglutide, attenuates intravenous self-administration of fentanyl in female rats.bioRxiv : the preprint server for biology · 2026Article
- Chronic semaglutide treatment enhances the incentive motivational value of a small food reward and associated cue in male and female rats.Psychopharmacology · 2026Article
- Incretin-Based Therapies: A Novel Pathway in Addiction Treatment.Journal of clinical medicine · 2026Review
- Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders.Frontiers in pharmacology · 2026Review
- Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon.Journal of internal medicine · 2025Review
- GLP-1 Therapeutics and Their Emerging Role in Alcohol and Substance Use Disorders: An Endocrinology Primer.Journal of the Endocrine Society · 2025Article
- Efficacy of the GLP-1 receptor agonist, semaglutide, in abstinence from illicit and nonprescribed opioids in an outpatient population with OUD: a randomized, double-blind, placebo-controlled clinical trial protocol.Addiction science & clinical practice · 2025Article
- Mechanisms of GLP-1 in Modulating Craving and Addiction: Neurobiological and Translational Insights.Medical sciences (Basel, Switzerland) · 2025Review
- An analysis on the role of glucagon-like peptide 1 receptor agonists in cognitive and mental health disorders.Nature. Mental health · 2025Article
- Effect of acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, and estrus phase on cue- and drug-induced fentanyl seeking in female rats.Behavioural pharmacology · 2025Article
- The Beneficial Effects of GLP-1 Receptor Agonists Other than Their Anti-Diabetic and Anti-Obesity Properties.Medicina (Kaunas, Lithuania) · 2024Review
- IUPHAR review - Glucagon-like peptide-1 (GLP-1) and substance use disorders: An emerging pharmacotherapeutic target.Pharmacological research · 2024Review
- Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.Addiction science & clinical practice · 2024Article
- PYYNeuropharmacology · 2023Article
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Chronic Semaglutide Treatment in Rats Leads to Daily Excessive Concentration-Dependent Sucrose Intake.Journal of the Endocrine Society · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
There has been a dramatic increase in illicit fentanyl use in the United States over the last decade. In 2018, more than 31,000 overdose deaths involved fentanyl or fentanyl analogs, highlighting an urgent need to identify effective treatments for fentanyl use disorder. An emerging literature shows that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the reinforcing efficacy of drugs of abuse. However, the effects of GLP-1R agonists on fentanyl-mediated behaviors are unknown. The first goal of this study was to determine if the GLP-1R agonist exendin-4 reduced fentanyl self-administration and the reinstatement of fentanyl-seeking behavior, an animal model of relapse, in rats. We found that systemic exendin-4 attenuated fentanyl taking and seeking at doses that also produced malaise-like effects in rats. To overcome these adverse effects and enhance the clinical potential of GLP-1R agonists, we recently developed a novel dual agonist of GLP-1Rs and neuropeptide Y2 receptors (Y2Rs), GEP44, that does not produce nausea-like behavior in drug-naïve rats or emesis in drug-naïve shrews. The second goal of this study was to determine if GEP44 reduced fentanyl self-administration and reinstatement with fewer adverse effects compared to exendin-4 alone. In contrast to exendin-4, GEP44 attenuated opioid taking and seeking at a dose that did not suppress food intake or produce adverse malaise-like effects in fentanyl-experienced rats. Taken together, these findings indicate a novel role for GLP-1Rs and Y2Rs in fentanyl reinforcement and highlight a potential new therapeutic approach to treating opioid use disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.