# Adaptations in Corticostriatal Networks in Alcohol Dependence Related Goal-Directed and Habitual Drinking

> **NIH NIH P50** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $178,871

## Abstract

PROJECT SUMMARY
The development of alcohol addiction is increasingly viewed as involving transition from controlled and
regulated consumption to uncontrolled drinking characterized as compulsive and habitual. Recent studies in
human alcoholics and animal models have suggested that chronic alcohol exposure may induce
neurobiological changes in corticostriatal circuits. These changes may underlie deficits in the ability to engage
goal-directed processes that normally function to suppress habitual actions. Consistent with this, evidence also
indicates that addiction is associated with an inability of the prefrontal cortex (PFC) to exert appropriate
inhibitory control over drug-taking and drug-seeking behaviors. Support for this comes from human imaging
studies that reveal alterations in prefrontal cortex and striatal brain regions in individuals with alcohol use
disorder (AUD) as compared to controls. Published and unpublished preliminary data further demonstrate that
chronic intermittent ethanol (CIE) exposure can facilitate the transition from flexible goal-directed drinking to
inflexible habitual drinking. Our preliminary data in mice demonstrates that CIE-induced facilitation of habitual
responding for alcohol can be reversed by chemogenetic inactivation of the infralimbic (IfL) cortex, a sub-region
of the mPFC that is roughly equivalent to the ventromedial PFC of humans. The overarching hypothesis of
this ARC research project is that repeated cycles of CIE exposure facilitates the expression of habitual
responding for alcohol, and that changes in activity of specific ensembles of neurons in the mPFC
plays a critical role in this process. It is further hypothesized that compromised dopamine (DA) modulation
of prefrontal function contributes to this CIE-induced transition to habitual drinking. The following three specific
aims will test this overarching hypothesis in the ARC mouse model of dependence-induced excessive, habit-
like drinking: Aim 1 will test the hypothesis that dependence-induced facilitation of habitual responding for
alcohol is associated with changes in population activity and network organization in the IfL cortex. Aim 2 will
test the hypothesis that DA D1 and D2 receptor-expressing neurons in the IfL cortex modulate dependence-
induced facilitation of the expression of habitual responding for alcohol. Aim 3 will test the hypothesis that
dependence-induced facilitation of habitual responding for alcohol is associated with alterations in the
biophysical properties of DA D1 and D2 receptor-expressing neurons in the IfL cortex. Together, these studies
will address the gap in our knowledge concerning the differential role of PFC-striatal subcircuits in the transition
from flexible goal-directed to inflexible habitual drinking, and will identify novel therapeutic targets for more
effective treatment of AUD.

## Key facts

- **NIH application ID:** 10329893
- **Project number:** 5P50AA010761-27
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** L Judson Chandler
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $178,871
- **Award type:** 5
- **Project period:** 1996-12-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329893

## Citation

> US National Institutes of Health, RePORTER application 10329893, Adaptations in Corticostriatal Networks in Alcohol Dependence Related Goal-Directed and Habitual Drinking (5P50AA010761-27). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10329893. Licensed CC0.

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