# GABAergic cortico-limbic circuit mechanisms of ethanol dependence

> **NIH NIH P60** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $267,916

## Abstract

Numerous studies have implicated adaptations in GABA signaling as a major factor in the pathogenesis of
alcohol dependence. Despite the established actions of ethanol on inhibitory control and GABAA receptors,
little is known about ethanol adaptations in GABAA receptor expression and signaling that occur in the medial
prefrontal cortex (mPFC) and central amygdala (CeA), interconnected brain regions that are implicated in the
development of alcohol dependence. Previous work has demonstrated significant adaptations in GABAA
receptor expression in cerebral cortex, cultured cortical neurons and CeA neurons, however the impact of
these changes on local microcircuitry and functional connectivity of the mPFC and CeA remain unclear. The
overarching goal of this component is to examine the role of GABAA receptor adaptations in overall circuit
function of mPFC and CeA following chronic ethanol exposure using electrophysiological, biochemical, and
molecular methods. We will further investigate the impact of histone deacetylases (HDACs) as the underlying
mechanism governing the GABAA receptor adaptations to determine the utility of HDAC inhibition as a potential
therapeutic target to selectively reverse pathological changes in GABAA receptor expression and circuit
function. We will also examine the effect of chronic ethanol exposure on functional connectivity between mPFC
and CeA using resting state functional magnetic resonance imaging (fMRI). Collectively, the proposed
studies will delineate molecular and cellular mechanisms of ethanol dependence in local mPFC and
amygdalar microcircuits as well as the mPFC projection to amygdalar subregions. These studies may
lead to microcircuit-specific molecular targets for reversal of ethanol dependence pathology.

## Key facts

- **NIH application ID:** 10078809
- **Project number:** 5P60AA011605-24
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** A LESLIE MORROW
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $267,916
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078809

## Citation

> US National Institutes of Health, RePORTER application 10078809, GABAergic cortico-limbic circuit mechanisms of ethanol dependence (5P60AA011605-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10078809. Licensed CC0.

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