# Analysis of subcortical networks that promote aversion-resistant alcohol drinking

> **NIH NIH R15** · MIAMI UNIVERSITY OXFORD · 2020 · $378,136

## Abstract

Project Summary
 Alcohol use disorder (AUD) is a debilitating and life-long addictive disease with significant public health
costs. Individuals suffering from AUD exhibit compulsive alcohol drinking, defined as drinking that is resistant
to negative or aversive consequences. While there is a growing recognition in the field of the need for more
relevant models of addictive behavior, there is still relatively little known about the neural circuits engaged
during compulsive drug seeking. Studies in humans and rats suggest a role for the nucleus accumbens (NAc)
core in compulsive-like alcohol drinking. D1-neurons are a subpopulation of neurons in the NAc that project to
the midbrain and the ventral pallidum (VP). Activity in D1-neurons is critical in controlling motivated and drug-
seeking behaviors. Convergent findings from preclinical models of alcohol dependence and obsessive-
compulsive disorder suggest the metabotropic glutamate receptor 5 (mGluR5) may play a role in biasing
striatal output toward D1-neurons. Given that alcohol exposure increases mGluR5 expression in the NAc,
mGluR5 expression on D1-neurons of the NAc core may serve as a key molecular contributor to compulsive-
like alcohol drinking. Our experiments will test this hypothesis through completion of two primary specific aims:
We will determine whether 1) mGluR5 expression on NAc core D1-neurons and 2) activity in D1-neuron
projections to the VP promote aversion-resistant alcohol drinking in mice. Aversion-resistant drinking will be
tested using a drinking in the dark model in which the bitter tastant quinine is added to ethanol. Collectively,
completion of these aims will characterize the contribution of mGluR5 on NAc core D1-neuron projections to
compulsive alcohol drinking, thereby delineating one of the mechanisms by which alcohol exposure can lead to
addictive behavior. Furthermore, we will train undergraduate students in a broad array of modern techniques in
behavioral neuroscience, such as chemogenetics, site-specific pharmacology, quantitative real-time PCR, and
flow cytometry. These activities will strengthen opportunities for behavioral neuroscience research at Miami
University and build institutional knowledge in the use of flow cytometry for neuroscience research.

## Key facts

- **NIH application ID:** 9965286
- **Project number:** 1R15AA027915-01A1
- **Recipient organization:** MIAMI UNIVERSITY OXFORD
- **Principal Investigator:** Anna Kay Radke
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,136
- **Award type:** 1
- **Project period:** 2020-09-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965286

## Citation

> US National Institutes of Health, RePORTER application 9965286, Analysis of subcortical networks that promote aversion-resistant alcohol drinking (1R15AA027915-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965286. Licensed CC0.

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