<span data-teams="true">A GPCR-Signaling Addiction Hub in the Murine Nucleus Accumbens and Its Partial Restitution by a GLP-1 Receptor Agonist: A Retrospective Transcriptomic Analysis
- Design
- Animal study · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: transcriptomic data from mouse nucleus accumbens, non-human evidence.
- Could weight loss explain it?
- PossiblyPossibly: no weight or glycaemic data are reported for the GLP-1 RA-treated mice; the evidence model's default applies, animal studies included.
- Study tier
- PreliminaryPRELIMINARY: a preprint, not peer reviewed; as a preclinical analysis it would otherwise be VERY_LOW.
- Assessment
- Version 2 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75. This item has not been peer reviewed.
This preprint re-analysed publicly available gene-expression data from a reward area of the mouse brain across models of opioid, cocaine, alcohol and food addiction, and from mice given a GLP-1 receptor agonist without any addiction. No single genes overlapped across the addictions, but a shared rise in a family of cell-signalling pathways was found, and the GLP-1 drug data showed an opposite pattern. Because the drug was not tested in addicted animals and these are mouse data, it does not show that GLP-1 drugs treat addiction.
01Findings
What the study reported
- Drugs
- Glp-1 receptor agonists
- Comparator
- not reported in abstract
- Primary outcome
- Shared nucleus accumbens transcriptomic signature across addictions and its restitution by a GLP-1 RA
- Effect
- No cross-addiction overlap at the individual gene level; enrichment analysis showed shared upregulation of GPCR signalling across addictions, with GLP-1 RA administration showing a discordant, restitutive signature; no numbers in the abstract
- 95% confidence interval
- not reported in abstract
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- Preprint re-analysis of public mouse RNA-seq datasets; the GLP-1 RA data come from addiction-naive animals, so reversal of the addiction signature is inferred across separate datasets rather than tested, and gene expression is not a behavioural or clinical outcome.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- mouse models of opioid, cocaine and alcohol use disorder and food addiction, plus an addiction-naive GLP-1 RA model
- Inclusion exclusion
- publicly available bulk RNA-seq datasets from mouse nucleus accumbens
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- n/a
- Comparator
- not reported in abstract
- Follow up duration
- not stated
- Outcome type
- biomarker
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- VERY_INDIRECT
- Statistical precision
- no CI, p values or sample counts reported
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- no
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Substance use disorders, including opioid use disorder, cocaine use disorder, alcohol use disorder, and behavioral disorders including food addiction, represent immense global health and economic burdens. Although initiated by distinct pharmacological mechanisms, these conditions converge on shared reward and compulsive neural circuitry within the mesocorticolimbic system, particularly the nucleus accumbens (NAc). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed for metabolic indications, have recently demonstrated activity in suppressing craving across multiple substance classes. We tested the hypothesis that there exists a shared transcriptomic hub across OUD, CUD, AUD, and FA that is restituted by GLP-1 RA. We conducted a retrospective transcriptomic analysis of publicly available bulk RNA-seq data from the murine NAc across these addictions, alongside an addiction-naive GLP-1 RA treatment model. At the individual gene level, cross-addiction overlap was not observed. Submitting top-ranked transcripts per condition to gene list enrichment and functional annotation analyses revealed shared upregulation of G-protein coupled receptor (GPCR) signaling with GLP-1 RA administration exhibiting a discordant, restitutive transcriptional signature. These findings demonstrate that in the murine NAc, diverse addictive substances converge on NAc GPCR overactivation with restitution of signaling, at least, in part, by a GLP-1 RA.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| europepmc | Oct 18, 2026 | PPR:PPR1340048 first ingestion |