# Synaptic Mechanisms of Nucleus Accumbens Disinhibition by Ethanol

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $495,298

## Abstract

Project Summary
 Alcohol misuse levies a major impact on public health, yet the brain mechanisms underlying how this
substance drives its misuse are poorly understood. This proposal seeks to discover a novel mechanism
underlying the rewarding properties of alcohol. Data derived from this study stand to provide novel treatment
strategies aimed at blunting the rewarding effects of alcohol in those suffering from alcohol use disorders. The
motivation to seek and acquire rewards is encoded by the output of a key reward integration center in the brain,
the nucleus accumbens. Inhibitory synapses in this structure powerfully gate its output. Our preliminary
experimentation indicates that alcohol pathologically disinhibits the nucleus accumbens by hijacking a form of
synaptic plasticity at inhibitory synapses. This novel mechanism positions alcohol as a pathological enhancer of
nucleus accumbens output and reward encoding. To elucidate this further, we propose three aims of
investigation using cutting-edge approaches: 1) to determine the neural circuit components necessary for driving
ethanol enhancement of this synaptic plasticity; 2) to determine the molecular mechanism mediating ethanol
enhancement of this form of plasticity and; 3) to causally determine how ethanol enhances NAc-iLTD reward
encoding in vivo. The results of this study stand to significantly advance our understanding of alcohol action in
the brain and provide important insight to myriad neuropsychiatric disorders involving nucleus accumbens
synaptic dysplasticity.

## Key facts

- **NIH application ID:** 10119082
- **Project number:** 1R01AA028070-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** BRIAN NEIL MATHUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $495,298
- **Award type:** 1
- **Project period:** 2021-01-20 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119082

## Citation

> US National Institutes of Health, RePORTER application 10119082, Synaptic Mechanisms of Nucleus Accumbens Disinhibition by Ethanol (1R01AA028070-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10119082. Licensed CC0.

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