# A critical role for rapid estrogen signaling in alcohol addiction and anxiety

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $440,444

## Abstract

Project Summary/Abstract
Binge alcohol drinking and high stress reactivity are leading risk factors for anxiety and alcohol use disorders,
and women are at twice the risk for co-expression of these diseases. The sex hormone estrogen has been
implicated in playing a modulatory role in anxiety and alcohol/drug use and may be related to the telescoping
of addiction observed in women by amplifying the positive and negative components of binge alcohol
consumption and withdrawal. Further, alcohol consumption itself may be able to stimulate estrogen synthesis
to promote drinking behavior, suggesting that estrogen signaling may be an important mechanism in addiction
for both males and females. However, the mechanisms by which estrogen regulates neuronal function to
control these behaviors is unknown. We hypothesize that estrogen signals at membrane-bound receptors
located at discrete synaptic nodes of limbic circuitry to modulate their control of behavior, and that this
mechanism is prominent at baseline in females but becomes more important in males across alcohol drinking
exposure. In the proposed work, we examine the locus and mechanism of endogenous estrogen signaling, its
effect on circuit function and corresponding behavior, and alcohol-induced plasticity in estrogen modulation in
both males and females.

## Key facts

- **NIH application ID:** 10447201
- **Project number:** 5R01AA027645-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Kristen Elizabeth Pleil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $440,444
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447201

## Citation

> US National Institutes of Health, RePORTER application 10447201, A critical role for rapid estrogen signaling in alcohol addiction and anxiety (5R01AA027645-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10447201. Licensed CC0.

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