# Doral raphe 5-HT neurons mediating estrogenic regulation of binge drinking

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $576,302

## Abstract

The ovarian hormone estrogen promotes binge drinking and contributes to sex differences in alcohol abuse.
Interestingly, we found an association between estrogen signaling and the brain serotonin (5-hydroxytryptamine,
5-HT) system, a key modulator of alcohol intake. For example, both estrogen receptor α (ERα) and β (ERβ) are
highly expressed in the 5-HT neurons in the dorsal raphe (5-HTDRN), the largest serotonergic neural population
and a major source of 5-HT. Notably, chronic binge-like ethanol intake led to sex-specific alterations in mRNA
expression of ERα and 5-HT-related genes in the DRN in mice, suggesting a potential role of estrogen/ERs/5-
HT signaling in binge drinking. Notably, we found that either ERα or ERβ agonist treatment attenuated the
stimulatory effects of alcohol on 5-HTDRN neurons, which may contribute to the higher levels of binge drinking in
females. We also showed that chemogenetic activation of ERαDRN or ERβDRN neurons reduced binge drinking in
female mice. These results support a model in which estrogen acts on ERα/β to prevent alcohol-induced
activation on 5-HTDRN neurons, leading to higher binge alcohol drinking. To test this hypothesis, we will pursue
three aims in the current grant. (1) We will test whether ERα and ERβ expressed by 5-HTDRN neurons are required
for estrogenic regulation of alcohol binge drinking. (2) We will determine whether estrogen signaling mediates
the sex dimorphic response of 5-HTDRN neurons to alcohol excitation. (3) We will determine the 5-HTDRN
downstream neural circuit that mediate the stimulatory effects of estrogens on alcohol binge drinking. Thus, the
proposed studies will be able to identify the specific receptor, neural population, neuronal firing, and neural circuit
mechanisms that mediate estrogens’ stimulatory effects on binge drinking. This proposal will investigate one of
the fundamental mechanisms contributing to the sex-dimorphism of excessive drinking. The results will provide
novel information for identifying new targets to develop more effective, individualized treatment for binge drinking
and alcohol-use disorders.

## Key facts

- **NIH application ID:** 10882340
- **Project number:** 1R01AA030880-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Pingwen Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $576,302
- **Award type:** 1
- **Project period:** 2024-05-17 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882340

## Citation

> US National Institutes of Health, RePORTER application 10882340, Doral raphe 5-HT neurons mediating estrogenic regulation of binge drinking (1R01AA030880-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10882340. Licensed CC0.

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