# Anterior insular cortex to dorsolateral striatum neural circuit regulation of binge drinking and habitual behaviors

> **NIH NIH F31** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $30,306

## Abstract

PROJECT SUMMARY
More than 14 million Americans currently have an alcohol use disorder (AUD) despite decades of research into
the effect of alcohol on the brain. One major hurdle to reducing the burden of AUD is understanding how
dysfunctions in the nervous system lead to the development and maintenance of alcohol addiction. To expand
our understanding of AUD, we must examine novel brain regions and neural circuits and directly probe these
targets with alcohol. A brain region of recent interest, the insula (insular cortex), has been heavily implicated in
the preoccupation/anticipation stage of the addiction cycle. A prior study in humans indicated that smokers who
acquired insula damage show reduced urges to smoke, the initial evidence for the insula’s role in the
preoccupation/anticipation stage of the addiction cycle. Yet, there is emerging evidence that the insular has an
expanded role in other stages of the addiction cycle. Thus, there is a critical need to investigate insular circuitry
to expand our understanding of neuroadaptations associated with AUD. Recently, our laboratory discovered a
connection between the anterior insular cortex (AIC) and the dorsolateral striatum (DLS) and established that
this circuit is uniquely sensitive to alcohol. While we know AIC-DLS circuit function displays alcohol sensitivity,
we do not know how this sensitivity alters alcohol-related behavioral sequences. My preliminary data indicates
that when AIC inputs to the DLS (AIC→DLS) are targeted with channelrhodopsin (ChR) and photoactivated
during oral alcohol consumption that mice decrease their alcohol intake during DID. I also find that
photoactivation does not induce real-time place preference, suggesting this circuitry is not directly modulating
valence states, but may be altering encoding and expression of habitual actions, both well-defined striatal-based
behaviors known to be altered by alcohol exposure. Together, these data suggest that the AIC plays a more
expansive and diverse role in the addiction cycle beyond the preoccupation/anticipation stage than previously
thought, but more work must be done to characterize alcohol-mediated AIC-DLS circuit changes. Aim 1 aims to
identify how AIC→DLS circuitry is altered by alcohol exposure and how modulating AIC→DLS circuits can alter
binge drinking behaviors. Aim 2 focuses on investigating how AIC→DLS circuits effect downstream medium
spiny projection neuron activity to modulate striatal-based behaviors such as habitual responding in both alcohol
naïve and alcohol exposed animals. Together, these data not only support an expanded role for the AIC as a
key mediator of neuroadaptations in AUD beyond the preoccupation/anticipation stage, but also elucidates
behavioral sequences governed by novel alcohol sensitive circuitry.

## Key facts

- **NIH application ID:** 10314186
- **Project number:** 1F31AA029297-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** David Leo Haggerty
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,306
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314186

## Citation

> US National Institutes of Health, RePORTER application 10314186, Anterior insular cortex to dorsolateral striatum neural circuit regulation of binge drinking and habitual behaviors (1F31AA029297-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10314186. Licensed CC0.

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