ArticleScience advances2025
An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Nucleus accumbens GLP-1 signaling and its role in reward and metabolic regulation: a systematic review.Frontiers in neuroanatomy · 2026Pooled it
- Glucagon-like peptide-1 receptor agonists for the treatment of opioid use disorders: a systematic review.Acta neuropsychiatrica · 2025Pooled it
- Decoding the Neural Circuit Underlying Context-Cue Association in Retrieval of Morphine Reward Memory.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association Between Baseline Glucagon-like Peptide-1 Receptor Agonist Use and Newly Documented Depression Diagnosis in Adults with Type 2 Diabetes: A Multi-State Medicaid Cohort Study.Healthcare (Basel, Switzerland) · 2026Article
- Dorsomedial striatal GABA dynamics organize palatable reward consumption and are reshaped by GLP-1 receptor agonism.bioRxiv : the preprint server for biology · 2026Article
- Resolution of anhedonia-like symptoms in patients treated for obesity with tirzepatide: A three-case series.Obesity pillars · 2026Article
- Review
- Glucagon-Like Peptide-1 Receptor Agonists in Cocaine Use Disorder: Clinical Observations and Underlying Mechanisms.Fundamental & clinical pharmacology · 2026Review
- Volitional cocaine taking engages distinct medium spiny neuron and astrocyte transcriptional programs in the rat nucleus accumbens.bioRxiv : the preprint server for biology · 2026Article
- Article
- Repeated semaglutide treatment attenuates cocaine-vs-food choice in male and female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Glucagon-like Peptide-1 and Dual GIP/GLP-1 Receptor Agonists in Brain: Exploring the Expanding Role and Safety in Neuropsychiatry.International journal of molecular sciences · 2026Review
- GLP-1 at the Metabolic-Cognitive Interface: Reward, Affect, and Memory.Comprehensive physiology · 2026Review
- 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
- Effects of chronic ethanol consumption on brain GLP-1R gene expression in mice and humans.Translational psychiatry · 2026Article
- The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events.Science advances · 2026Article
- Off-label and investigational drugs in the treatment of gambling disorder: a critical review.Frontiers in pharmacology · 2026Review
- The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Pain Management in Chronic Pancreatitis: A Real-World Cohort Study.Gastro hep advances · 2026Article
- Chemical multiplexing in the nervous system: molecular architecture, functional stratification, and pathophysiological plasticity of neuropeptide-classical neurotransmitter cotransmission.Frontiers in molecular neuroscience · 2026Review
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Abstract
Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate cocaine seeking. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius that project to the ventral tegmental area (VTA) decreased cocaine seeking. Single-nuclei transcriptomics and FISH studies revealed that GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.
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