# Epigenetic regulation of stress-potentiated ethanol drinking

> **NIH AA R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2026 · $398,823

## Abstract

Epigenetic Regulation of Stress-Potentiated Ethanol Drinking
PROJECT SUMMARY/ABSTRACT
A common mechanism that regulates both stress-sensitivity and alcohol use is epigenetic regulation of gene
transcription. Of particular importance in substance-use disorders is G9a, a histone methyltransferase implicated
in models of alcohol use disorder (AUD). G9a in the nucleus accumbens (NAc) regulates drinking, but its
mechanisms are unknown. The long-term goal of this project is to elucidate the mechanisms that can lead to
stress-potentiated drinking and to discover methods to block or reverse these changes. Because the dynorphin
system plays a prominent role in stress and ethanol-related behaviors, and dynorphin is present in a major subset
of NAc neurons, Aim 1 will test the hypothesis that NAc G9a’s effects on stress-potentiated ethanol drinking are
mediated through dynorphin-positive neurons (NAcDyn+). This hypothesis will be tested by using a novel Cre-
dependent shRNA viral vector and a novel Cre-dependent G9a over-expression viral vector in both dynorphin-
Cre mice and enkephalin-Cre mice. Specifically, G9a will be knocked down or overexpressed in these NAc
neuronal subsets, and the effects of G9a will be tested on two different forms of stress-potentiated drinking. We
will also examine the NAc subregions involved in G9a’s effects. Next, Aim 2 will test the hypothesis that the
mechanism underlying G9a’s effects on stress-potentiated ethanol drinking involve NAc intrinsic excitability by
altering the expression of a specific potassium (K+) channel subunit. The hypothesis for Aim 2 is that the effects
of G9a on this K+ channel subunit reduces stress-potentiated drinking. We will directly test G9a’s ability to
regulate this K+ channel subunit with a CRISPR-fused G9a, and we will test G9a’s effects on transcription and
chromatin state using single nuclei multiomics. Finally, Aim 3 will test the hypothesis that the effects of NAc G9a
on stress-potentiated ethanol drinking ar

## Key facts

- **NIH application ID:** 11392212
- **Project number:** 5R01AA031007-02
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Ethan Michael Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AA
- **Fiscal year:** 2026
- **Award amount:** $398,823
- **Award type:** 5
- **Project period:** 2025-08-15T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11392212

## Citation

> US National Institutes of Health, RePORTER application 11392212, Epigenetic regulation of stress-potentiated ethanol drinking (5R01AA031007-02). Retrieved via AI Analytics 2026-06-29 from https://api.ai-analytics.org/grant/nih/11392212. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*