ArticleTranslational psychiatry2016
Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side.Frontiers in neuroscience · 2021Pooled it
- Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol.Frontiers in behavioral neuroscience · 2020Pooled it
- Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption.Alcohol, clinical & experimental research · 2025Trial
- Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial.JCI insight · 2022Trial
- Glucagon-Like Peptide-1 Receptor Agonists in Cocaine Use Disorder: Clinical Observations and Underlying Mechanisms.Fundamental & clinical pharmacology · 2026Review
- Glucose-Dependent Insulinotropic Polypeptide Receptors Are Expressed in the Lateral Septum and Reduce Electrically-Evoked Dopamine Release as well as the Ability of Cocaine to Increase Extracellular Dopamine.ACS chemical neuroscience · 2026Article
- Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.Biochemistry and biophysics reports · 2026Article
- Tirzepatide attenuates mesolimbic cocaine-evoked dopamine levels and reduces cocaine taking, motivation and seeking behaviours in male rodents.EBioMedicine · 2026Article
- Incretin-Based Therapies: A Novel Pathway in Addiction Treatment.Journal of clinical medicine · 2026Review
- Diet-induced obesity impairs refeeding responses and downregulates lateral septal GLP-1R in male rats: an effect reversed by weight-loss treatment.Frontiers in pharmacology · 2026Article
- Time-restricted feeding promotes glucagon-like peptide-1 secretion and regulates appetite via tryptophan metabolism of gutGut microbes · 2025Article
- GLP-1 Therapeutics and Their Emerging Role in Alcohol and Substance Use Disorders: An Endocrinology Primer.Journal of the Endocrine Society · 2025Article
- The GLP-1R Agonist Semaglutide Reduces Motivated Running and Alters Dopamine Dynamics in the Nucleus Accumbens.bioRxiv : the preprint server for biology · 2025Article
- GLP-1 Analogues in the Neurobiology of Addiction: Translational Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies.Diabetes & metabolism journal · 2025Review
- Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.Basic & clinical pharmacology & toxicology · 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
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Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA.
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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.