The GLP-1 receptor agonist semaglutide reduces alcohol consumption and anxiety-like behaviors during withdrawal in Marchigian Sardinian alcohol-preferring rats
- Design
- Animal study · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: the study is in Marchigian Sardinian alcohol-preferring rats, a bred animal model, not in people.
- Could weight loss explain it?
- PossiblyPossibly: the record itself reports that semaglutide lowered blood glucose and decreased fat mass in naïve animals, and nothing separates those metabolic changes from the fall in alcohol intake or the anxiolytic-like behaviour. No mediation analysis, weight-matched comparison or measurement before weight change is reported.
- Study tier
- Study tier 4VERY_LOW: a preclinical animal experiment, which sits at study tier 4; the abstract also gives no animal numbers, effect sizes, intervals or p values.
- Assessment
- Version 3 · Two independent AI reviews agreed · Nov 6, 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.
Male and female Marchigian Sardinian alcohol-preferring rats, a line bred to drink heavily and to be anxious, were given semaglutide under the skin at 0.001, 0.01 or 0.1 mg/kg, or vehicle. Semaglutide cut voluntary alcohol drinking dose by dose and reduced anxiety-like behaviour during withdrawal. In rats not drinking alcohol it also lowered movement and blood glucose, reduced fat mass, and damped GABA signalling in one part of the prefrontal cortex. The abstract reports no animal numbers, effect sizes or statistics, and this is animal evidence, not evidence in people.
01Findings
What the study reported
- Drugs
- Semaglutide
- Dose
- 0.001, 0.01 and 0.1 mg/kg
- Route
- subcutaneous
- Comparator
- vehicle
- Primary outcome
- voluntary alcohol consumption in the two-bottle choice paradigm, with anxiety-related behaviour during withdrawal
- Effect
- No numerical estimates are given. Semaglutide reduced voluntary alcohol consumption dose-dependently and produced anxiolytic-like behaviour during withdrawal in the open field test; in naïve animals it reduced locomotor activity, lowered blood glucose, and decreased fat mass and GABAergic transmission in the infralimbic medial prefrontal cortex.
- 95% confidence interval
- not reported in abstract
- Follow-up
- Not stated
- Adverse events
- In naïve animals semaglutide reduced locomotor activity, lowered blood glucose levels, and decreased fat mass and GABAergic transmission in the infralimbic medial prefrontal cortex; no other safety findings are reported.
- Limitations
- Animal study in a selectively bred alcohol-preferring rat line, with no animal numbers, effect sizes or statistics in the abstract and no randomization or blinding described; semaglutide reduced locomotor activity at the dose used for the behavioural tests, which could affect those readouts. The authors state no limitations.
Who was studied
- Sex distribution
- male and female rats
- 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
- Marchigian Sardinian alcohol-preferring rats, a line with excessive alcohol intake and pronounced anxious and depressive-like phenotypes
- Inclusion exclusion
- male and female Marchigian Sardinian alcohol-preferring rats; naïve rats for the locomotor, stress and electrophysiology experiments
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- vehicle
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- VERY_INDIRECT
- Statistical precision
- no estimates, confidence intervals, p values or animal numbers reported
- Risk of bias
- not assessed
- Peer review status
- yes
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
- Authors declare no known competing financial interests or personal relationships that could have influenced the work.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising pharmacotherapeutics for alcohol use disorder (AUD). Here, we examined the effects of semaglutide, a long-acting GLP-1 receptor agonist, on alcohol intake and anxiety-related behaviors in Marchigian Sardinian alcohol-preferring rats, a model characterized by excessive alcohol intake and pronounced anxious and depressive-like phenotypes. Male and female rats were treated with semaglutide (0.001, 0.01 and 0.1 mg/kg, s.c.) and vehicle. Voluntary alcohol consumption was assessed using the two-bottle choice paradigm. Locomotion, anxiety, and stress responses were evaluated during withdrawal and in naïve rats, following administration of the highest dose of semaglutide (0.1 mg/kg). Furthermore, the acute effects of semaglutide on GABAergic transmission were assessed in the central nucleus of the amygdala and in the infralimbic (IL) medial pre-frontal cortex (mPFC) of naïve rats. Semaglutide reduced voluntary alcohol consumption in a dose-dependent manner, and it produced anxiolytic-like behaviors during withdrawal in the open field test. In naïve animals, semaglutide reduced locomotor activity, lowered blood glucose levels, and decreased fat mass and GABAergic transmission in the IL mPFC. Our findings support the use of the GLP-1 receptor agonist semaglutide as a promising pharmacotherapy for the treatment of AUD and its associated psychiatric symptoms.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Nov 1, 2026 | 42946204 first ingestion |
| owner-review | Nov 6, 2026 | reviewed_by set to Carrie Schluter (2026-11-05) on the owner's own confirmation. The assessment is unchanged and still the auto-classifier's, so its extracted values stay withheld under the 2026-10-18 decision. |
| reextract | Nov 6, 2026 | dose: '0.1 mg' -> '0.001 mg/kg, 0.01 mg/kg, 0.1 mg/kg'. Q-043: manufacturer and drug_details.dose re-extracted by auto-classifier-v1.2. manufacturer no longer reads companies named only in the authors' conflicts statement (IN-062) and refuses a multi-company roster; dose is tied to the GLP-1 agent by name, never reads a concentration, and records a multi-dose design whole. Every other value is carried forward unchanged. Owner decision IN-064 option 1, 2026-11-06. |
| pubmed | Nov 8, 2026 | 42946204 duplicate matched on doi |