# Role of Central Amygdala Astrocyte Plasticity in Ethanol Dependence

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $46,752

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol use disorder (AUD) affects over 16 million Americans, contributes to millions of preventable deaths, and
causes enormous financial and societal burdens. Therefore, gaining a better understanding of the
neurobiological mechanisms underlying AUD would provide insight for developing improved therapeutic
strategies. Alcohol (ethanol) dependence is a hallmark of AUD that is characterized by excessive alcohol intake,
somatic withdrawal symptoms, and negative mood. The central nucleus of the amygdala (CeA) is a key brain
structure involved in ethanol dependence. For example, synaptic transmission is dysregulated in the CeA
following chronic ethanol exposure and CeA activity is required for escalated ethanol drinking and withdrawal
symptoms during dependence. Accumulating evidence suggests that astroglial cells are essential regulators of
synaptic transmission and behavior, however, we lack a basic understanding regarding the role of astrocytes in
in ethanol dependence. Two particularly important questions are 1) how does chronic ethanol exposure affect
astrocyte-neuron interactions and 2) do astrocytes have a causal role in regulating the consequences of ethanol
dependence and withdrawal. The proposed studies will begin to address these questions by testing the
overarching hypothesis that chronic ethanol exposure alters astrocyte-synapse proximity in the CeA and the
astrocytic GABA transporter, GAT3, mediates ethanol withdrawal and dependence-escalated ethanol intake.
The experimental approach utilizes a rat model of chronic intermittent ethanol (CIE) exposure by vapor inhalation
and ethanol drinking in combination with super resolution confocal microscopy and three-dimensional astrocyte
morphology analysis. The overarching hypothesis will be tested in the following two specific aims. Aim 1 will test
the hypothesis that chronic ethanol exposure modulates astrocyte-neuron interactions in the CeA. Astrocyte-
synapse proximity will be assessed following CIE exposure to determine the temporal properties of changes in
astrocyte plasticity. Astrocyte-synapse proximity will also be assessed following ethanol access during
withdrawal to determine how voluntary ethanol drinking modulates astrocyte plasticity in dependent and non-
dependent rats. Aim 2 will test the hypothesis that astrocytic GAT3 in the CeA regulates dependence-escalated
ethanol intake and somatic withdrawal. A morpholino antisense oligonucleotide strategy will be used to
knockdown GAT3 in the CeA to determine whether GAT3 is necessary for the expression of escalated ethanol
intake and somatic withdrawal during ethanol dependence. In contrast, a viral overexpression strategy will be
used to increase astrocytic GAT3 expression in the CeA to determine whether GAT3 is sufficient to modulate
escalated ethanol intake and withdrawal. The consequences of GAT3 manipulation on astrocyte plasticity will
also be assessed. Together, these studies will provide novel insight i...

## Key facts

- **NIH application ID:** 10447003
- **Project number:** 5F31AA029622-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Todd B Nentwig
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447003

## Citation

> US National Institutes of Health, RePORTER application 10447003, Role of Central Amygdala Astrocyte Plasticity in Ethanol Dependence (5F31AA029622-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447003. Licensed CC0.

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