# Dietary choline mitigation of adolescent alcohol-induced deficits in adult cognitive flexibility: P60-AA011605 Administrative Supplement

> **NIH NIH P60** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $155,500

## Abstract

Abstract:
This is an administrative supplement to P60-AA011605 “Molecular and Circuit Pathogenesis of
Alcohol Addiction” in response to PA-20-227 “Administrative Supplements for Research on
Dietary Supplements (Admin Supp Clinical Trial Not Allowed).” The supplement will add an aim
to Project 3, “Frontolimbic circuitry, behavioral flexibility, and adolescent alcohol history.” The
parent project investigates how adolescent binge drinking (humans) or ethanol exposure (rats)
impairs behavioral flexibility, with effects persisting into adulthood. We use a unique
translational approach to probe the neurobiological bases of the ability to form and to flexibly
overcome automatic actions and to evaluate theoretically based interventions to bidirectionally
modulate behavioral flexibility. Our core hypothesis is that adolescent binge alcohol exposure
promotes both an overreliance on stimulus-response action selection strategy (habit) and
hypersensitivity to reward conditioning in adulthood via common alterations in shared underlying
neural circuits. Moreover, the relationship between reliance on habit and sensitivity to reward
conditioning is mediated by neural circuit changes impairing top-down control of responses to
salient exogenous cues. The parent project uses resting-state fMRI and electrophysiology to
identify differences in brain circuit function associated with impairment in overriding automatic S-
R associations and sensitivity to reward conditioning. It also tests whether bidirectional
manipulation of frontal cortex can promote or reduce top-down control over behavior, thereby
ameliorating or mimicking the impairment associated with adolescent alcohol exposure. This
supplement adds an aim to determine whether dietary choline supplementation can prevent or
reverse the impairments in behavioral flexibility and associated neurochemistry induced by
adolescent ethanol exposure. Overall, this work will identify objective targets for use in
developing novel treatments to promote flexible, goal-directed actions over deleterious
automatic actions. This approach may substantially improve our ability to cope with the public
health challenges of AUDs, a leading cause worldwide of preventable death.

## Key facts

- **NIH application ID:** 10330051
- **Project number:** 3P60AA011605-24S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Thomas L. Kash
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,500
- **Award type:** 3
- **Project period:** 2021-07-20 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330051

## Citation

> US National Institutes of Health, RePORTER application 10330051, Dietary choline mitigation of adolescent alcohol-induced deficits in adult cognitive flexibility: P60-AA011605 Administrative Supplement (3P60AA011605-24S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10330051. Licensed CC0.

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