ArticleMolecular psychiatry2023
Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases.mSystems · 2024Pooled it
- Efficacy of WeChat-Based Digital Intervention Versus Metformin in Women With Polycystic Ovary Syndrome: Randomized Controlled Trial.Journal of medical Internet research · 2024 · on this mapTrial
- SCTR-Expressing Astrocyte-Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac-Foxc2 Epigenetic Axis in an AMPK-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GABA as an Overlooked Mediator of Metformin Action: GABA-mediated Neuropsychiatric and Hepatoprotective Activities of Metformin.Annals of neurosciences · 2026Review
- Standardized chronic restraint stress protocols reveal dynamic evolution of behavioral adaptations in male mice: implications for translational neuroscience.Molecular psychiatry · 2026Article
- Medium-intensity aerobic exercise can relieve mice anxiety by activating cannabinoid type 1 receptors on medial prefrontal cortex GABAergic neurons.Translational psychiatry · 2026Article
- Cordycepin alleviates nicotine withdrawal-induced anxietyDrug and alcohol dependence reports · 2026Article
- Metformin reverses oxandrolone-induced anxiety-like behavior and amygdalar neurochemical dysregulation in male rats.Psychopharmacology · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Toward a gut-AMPK axis: the microbiome and AMPK signaling in nutrition and healthy aging.Frontiers in physiology · 2026Review
- Cascade-targeting pH/ROS microneedles promote scarless diabetic wound healing by macrophage metaboimmune reprogramming.Science advances · 2025Article
- Biomimetic ferritin nanocages for synergistic co-delivery of metformin and rapamycin restore neurodevelopmental homeostasis in autism spectrum disorders.Journal of nanobiotechnology · 2025Article
- Repurposing Caffeine, Metformin, and Furosemide to Target Schizophrenia-Related Impairments in a Triple-Hit Rat Model.International journal of molecular sciences · 2025Article
- Neuronal CCL2 responds to hyperglycaemia and contributes to anxiety disorders in the context of diabetes.Nature metabolism · 2025Article
- Metformin's Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review.International journal of molecular sciences · 2025Review
- Sex differences in cognition, anxiety-phenotype and therapeutic effect of metformin in the aged apoE-TR mice.Biology of sex differences · 2025Article
- Deletion ofFrontiers in behavioral neuroscience · 2025Article
- Article
- Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.
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