Translational psychiatryJan 30, 2026

Long-term alcohol use linked to changes in brain GLP-1 receptor gene expression in mice and humans

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Feb 1, 2026

Abstract

GLP-1R gene expression was significantly reduced in all brain regions of ethanol-exposed mice and patients with alcohol use disorder (AUD).

Chronic alcohol consumption for 42 days in mice led to decreased GLP-1R gene expression in the prefrontal cortex, nucleus accumbens, and hippocampus.
Postmortem samples from 18 patients with AUD also showed significant reductions in GLP-1R gene expression in similar brain regions.
Decreased GLP-1R expression was associated with reduced levels of the mu-opioid receptor (OPRM1) in the nucleus accumbens and brain-derived neurotrophic factor (BDNF) in the hippocampus.
No significant correlations were found between gene expression and various clinical parameters, including age and body mass index.
Findings suggest that chronic alcohol exposure may negatively impact GLP-1R gene expression in brain regions related to alcohol's rewarding effects.

Simplified

The glucagon-like peptide-1 receptor (GLP-1R) has emerged as a promising therapeutic option for alcohol use disorder (AUD), yet the underlying mechanisms and neurocircuitry involved remain unclear. This study aimed to analyze GLP-1R gene expression changes in brain regions associated with alcohol's effects, including the prefrontal cortex (PFC), nucleus accumbens (NAc), and hippocampus (HIP), in mice following 42 days of voluntary ethanol consumption (VEC; 10% v/v) and postmortem samples from 18 patients with AUD. Additionally, we examined the expression of OPRM1 (mu-opioid receptor) and BDNF (brain-derived neurotrophic factor), key targets related to alcohol intake and reward, in the NAc and HIP, respectively. GLP-1R gene expression was significantly reduced in all brain regions of ethanol-exposed mice and AUD patients. These reductions paralleled decreased OPRM1 and BDNF expression in the NAc and HIP, respectively. Pearson and Spearman correlation analyses revealed no significant associations between gene expression and age, RIN, pH, postmortem interval (PMI), body mass index (BMI), smoking status, age of onset of alcohol use, or years of drinking. In summary, chronic alcohol consumption in humans or mice was associated with decreased GLP-1R gene expression in brain regions involved in the reinforcing effects of ethanol. These findings open new avenues for further research into how this emerging receptor could serve as a potential biomarker and therapeutic target in AUD.

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Funding

Competing interests

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. All animal procedures were approved by the Ethics and Research Integrity Committee of Miguel Hernández University (approval number: UMH.IN.JM.01.21) and were conducted in accordance with institutional and national guidelines for the care and use of laboratory animals. Human samples were obtained from the New South Wales Tissue Resource Centre (NSWBTRC) at the University of Sydney, Australia. The use of these samples was approved by the Ethics and Research Integrity Committee of Miguel Hernández University (approval number: IN-JM-001-11), in accordance with the biobank’s governance procedures. Written informed consent was obtained from all participants prior to sample collection.

PubMed

Long-term alcohol use linked to changes in brain GLP-1 receptor gene expression in mice and humans

Abstract

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Abstract

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