Selective dysregulation of serotonin dynamics in the anterior cingulate cortex and central amygdala following binge alcohol consumption

Sep 30, 2026

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Serotonin (5HT) is a critical modulator of brain function and behavior, dysregulated in alcohol use disorder (AUD). The anterior cingulate cortex (ACC) and central nucleus of the amygdala (CeA) show distinct roles in AUD and undergo functional changes after binge drinking, yet real-time 5HT dynamics remain unclear. Using fiber photometry with the GRAB5HT sensor, the study reveals region-specific reward and aversion 5HT signaling, with non-uniform, sex- and stimulus-specific dysfunction shifting across weeks of alcohol experience.

LanguageEnglish

CategoryResearch & Report

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Pages26

Reading Time1 h 6 min

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Abstract

Hypothesis and approach

Key findings: reward and aversion motifs

Behavioral and circuit-level implications

bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.19.695484](https://doi.org/10.64898/2025.12.19.695484); this version posted December 22, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Selective dysregulation of serotonin dynamics in the anterior cingulate cortex and central amygdala following binge alcohol consumption Jobe L Ritchie 1, Maya R Eberle1, Alison Roland1, Lisa Taxier1, Madison Campeau1, Brianna George1, Lili Kooyman1, Thomas L Kash1,2 1 Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 2 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Corresponding author: Dr. Thomas Kash, [tkash@email.unc.edu](tkash@email.unc.edu) [Running title: Alterations in 5HT dynamics following binge drinking](Running title: Alterations in 5HT dynamics following binge drinking) Keywords: binge drinking, 5HT/serotonin, anterior cingulate cortex, central nucleus of the amygdala, fiber photometry Declaration of Interests: The authors have nothing to declare. Funding: This research was supported by grants from the National Institutes of Health’s (NIH) R01AA022048 and T32AA007573 . bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.19.695484](https://doi.org/10.64898/2025.12.19.695484); this version posted December 22, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Serotonin (5HT) is a critical modulator of brain function and behavior that is dysregulated in alcohol use disorder (AUD) . The anterior cingulate cortex (ACC) and central nucleus of the amygdala (CeA) play distinct roles inAUD and undergo functional changes in 5HT signaling following binge drinking, but our understanding of real-time 5HT dynamics in these structures is lacking. We hypothesized that binge drinking would elicit brain-region specific dysfunction in 5HT dynamics during appetitive and aversive stimuli processing. Using fiber photometry with the GRAB5HT sensor, we identified distinct reward and aversion 5HT signaling motifs in the ACC and CeA. Consumption of alcohol and other tastants elicited a suppression of GRAB5HT signal in the ACC and an increase in 5HT signal in the CeA. In contrast, aversive stimuli similarly increased 5HT in both structures. The effect of binge drinking on 5HT function was surprisingly non-uniform, producing brain-region, sex- , and stimulus-specific dysfunction in 5HT signaling that dramatically shifted across weeks of alcohol experience. This suggests that adaptations in 5HT signaling are specific to neural circuits underlying discrete functions. Optogenetically stimulating 5HT terminals in the ACC and CeA increased avoidance behavior without being overtly rewarding or aversive, and stimulating 5HT release in the ACC blunted alcohol drinking. Together, these data identify distinct 5HT reward and aversion signaling motifs in the ACC and CeA and highlight early binge drinking as a critical stage of 5HT adaptation and a potential window for therapeutic intervention. bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.19.695484](https://doi.org/10.64898/2025.12.19.695484); this version posted December 22, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Introduction Alcohol misuse is associated with negative affective states, dysregulated reward processing , and a heightened risk for the development of an alcohol use diso

FAQs

What brain regions were studied for 5HT dynamics after binge drinking?

The anterior cingulate cortex (ACC) and the central nucleus of the amygdala (CeA) were investigated for real-time serotonin signaling changes following binge alcohol consumption.

How did binge alcohol consumption affect 5HT signaling during appetitive versus aversive processing?

Alcohol and other tastants suppressed GRAB5HT signal in the ACC and increased 5HT signal in the CeA, while aversive stimuli increased 5HT in both regions.

What does the study suggest about how 5HT adaptations develop over time with binge drinking?

The effects of binge drinking on 5HT function were non-uniform, showing brain-region, sex-, and stimulus-specific dysfunction that dramatically shifted across weeks of alcohol experience.

Sep 30, 2026

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