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Orbitofrontal BDNF puts the brakes on alcohol intake and relapse

Neuropsychopharmacology volume 51, pages 552–553 (2026)Cite this article

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Alcohol Use Disorder (AUD) is a severe disease that is expressed by uncontrolled drinking despite negative consequences. Since only a small percentage of moderate social drinkers typically develop AUD, it is likely that there are protective mechanisms that mitigate the development of neuroadaptations that lead to addiction. Over the past 20 years, cortical brain-derived neurotrophic factor (BDNF) has been shown to counteract the development of cellular/molecular neuroadaptations underlying addiction in animal models, including AUD. BDNF is a neuropeptide that mediates structural and functional neuroplasticity in many brain circuits, particularly in cerebral cortical pathways.

Prior work by many laboratories, including the Ron lab, indicates that neuroadaptations that accompany heavy alcohol intake result from dysfunctional BDNF signaling, especially in the prefrontal cortex (PFC). PFC is a heterogeneous brain region that regulates cognitive decision-making and impulsive behaviors. Excessive alcohol drinking leading to dependence causes a persistent reduction in BDNF mRNA and protein in the prelimbic region of the medial PFC [1]. Increasing BDNF in the medial prefrontal cortex (mPFC) by direct infusion or viral-mediated overexpression blocks binge-like drinking in alcohol-dependent mice [1]. A polymorphism (BDNfVal66Met) in the bdnf gene that disrupts BDNF release causes compulsive (quinine-resistant) alcohol drinking and a preference of alcohol over water in mice [2].

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References

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  1. Dept of Neuroscience, Medical University of South Carolina, Charleston, SC, USA

    Jacqueline F. McGinty

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  1. Jacqueline F. McGinty
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Correspondence to Jacqueline F. McGinty.

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McGinty, J.F. Orbitofrontal BDNF puts the brakes on alcohol intake and relapse. Neuropsychopharmacol. 51, 552–553 (2026). https://doi.org/10.1038/s41386-025-02290-1

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