# Novel mechanism of alcohol self-administration and relapse

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $349,875

## Abstract

Project Summary
Pathological alcohol-seeking behavior is regulated in part by glutamate AMPA receptor (AMPAR)
activity in the amygdala. Transmembrane AMPA receptor regulatory proteins (TARPs) profoundly
affect the trafficking and function of AMPARs in synaptic and behavioral plasticity. Although the
TARP family of proteins is expressed throughout the brain, the TARP γ-8 subtype is restricted to
forebrain regions including the basolateral amygdala (BLA); a brain region that is critical to
addiction. However, the role of TARP γ-8 in alcohol use disorders (AUD) or other addictions is
unknown. To fill this gap in knowledge, we propose an innovative set of behavioral, genetic,
bidirectional systemic and site-specific pharmacological, molecular, and physiological studies in
mice to evaluate the mechanistic role of TARP γ-8 in alcohol reinforcement, escalated self-
administration, and cue-induced reinstatement of alcohol-seeking behavior as a model of relapse.
Elucidating the neural mechanisms of these three critical behavioral domains has high
translational value for understanding the development, progression, and maintenance of AUD.
Successful completion of the studies in this application will provide fundamental mechanistic
insights into TARP γ-8 regulation of pathological alcohol-seeking behavior. Moreover, this work
moves the field forward in understanding the molecular mechanisms by which alcohol hijacks
reward processes and has potential to inform development of new pharmacotherapeutic
strategies that target AMPAR function in a highly selective brain region-specific manner.

## Key facts

- **NIH application ID:** 10817187
- **Project number:** 5R01AA028782-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Clyde W Hodge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2021-05-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817187

## Citation

> US National Institutes of Health, RePORTER application 10817187, Novel mechanism of alcohol self-administration and relapse (5R01AA028782-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10817187. Licensed CC0.

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