# Mechanisms of alcohol-induced plasticitey mediated by Arf6

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $343,125

## Abstract

Alcohol abuse disorders (AUD) are a major health hazard that affects millions of people every year in the
United States. Repeat alcohol exposure can lead to tolerance, increased preference and consumption. Such
behavioral changes, and the accompanying neuronal plasticity, underlie addiction, yet many molecular
mechanisms governing these changes remain to be elucidated. Signaling through the insulin receptor (InR) in
neurons is known to modify plasticity, but its effects on alcohol-induced behavioral responses are not known.
Our goal is to understand the cellular, neural, and circuit mechanisms of Arf6-dependent nervous system InR
signaling in alcohol-induced plasticity. This is based on our published data that Arf6 mediates InR signaling in
vivo and in cell culture. First, we will determine the mechanisms of Arf6-mediated InR signaling and
endocytosis. We will systematically, and comprehensively test the role of two gene families known to directly
regulate the function of Arf6. Second, we will determine neural circuits that specifically affect ethanol-induced
tolerance and consumption preference, as well as the naïve aversive reactions to alcohol. We will test the role
of Arf6 regulators in these circuits in alcohol-induced behavioral responses. Third, we will determine in vivo
mechanisms how signaling from the InR pathway can affect distinct alcohol-induced behavioral changes:
tolerance, and consumption preference. The genes we propose to investigate are all conserved from
Drosophila to humans, and the proposed research will advance our molecular understanding of the
mechanisms regulating alcohol-induced behavioral changes. This in turn, will result in the identification of new
risk factors and therapeutic targets for the treatment of alcohol abuse disorders.

## Key facts

- **NIH application ID:** 9941007
- **Project number:** 5R01AA026818-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adrian Rothenfluh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 2018-08-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941007

## Citation

> US National Institutes of Health, RePORTER application 9941007, Mechanisms of alcohol-induced plasticitey mediated by Arf6 (5R01AA026818-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9941007. Licensed CC0.

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