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Septal GLP-1 receptors control alcohol taking and seeking
Ginevra D'Ottavio1, Kenichiro Negishi1, Yavin Shaham1
1Behavioral Neuroscience Branch, Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.
Neuron
|July 1, 2026
Summary
Glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide reduces alcohol consumption in rodents. This effect is mediated by a GABAergic microcircuit in the lateral septum that expresses GLP-1 receptors.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Alcohol use disorder is a significant public health concern.
- Glucagon-like peptide-1 (GLP-1) receptor agonists have shown potential in modulating addictive behaviors.
- The neural circuits underlying GLP-1 receptor-mediated effects on alcohol intake are not fully understood.
Purpose of the Study:
- To investigate the neural mechanisms by which GLP-1 receptor agonists inhibit alcohol intake.
- To identify specific brain regions and neuronal populations involved in this effect.
- To elucidate the role of GABAergic signaling in the lateral septum.
Main Methods:
- Systemic administration of liraglutide, a GLP-1 receptor agonist.
- Electrophysiological recordings in rodent models.
- Optogenetic and chemogenetic manipulation of neuronal activity.
- Analysis of alcohol consumption behavior.
Main Results:
- Liraglutide administration significantly reduced alcohol intake in rodent models.
- GLP-1 receptor-expressing neurons in the lateral septum were identified as key mediators.
- Activation of a specific GABAergic microcircuit within the lateral septum was observed.
- Inhibition of this microcircuit mimicked the effects of liraglutide on alcohol intake.
Conclusions:
- A lateral septum GABAergic microcircuit plays a critical role in regulating alcohol consumption.
- GLP-1 receptor signaling in this microcircuit mediates the inhibitory effects of liraglutide on alcohol intake.
- Targeting this circuit may offer a novel therapeutic strategy for alcohol use disorder.
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