# Center on Genetic Determinants of Alcohol Ingestion and Responses to Alcohol

> **NIH NIH P60** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $1,663,064

## Abstract

Project Summary: Overall Indiana Alcohol Research Center (IARC)
 The Indiana Alcohol Research Center (IARC) has devoted three decades to understanding how genetic
factors and responses to alcohol contribute to the risk of developing an alcohol use disorder (AUD). We
continue these efforts by now examining why certain immoderate drinkers transition into a stage in which they
become insensitive to the aversive outcomes associated with heavy drinking. The IARC will therefore address
the critical need to understand the genetic, behavioral, and neurobiological paths by which “aversion-resistant
drinking” develops. The rationale for our centered approach is that working in close association across several
scientific disciplines and spheres of expertise permits our investigators to achieve insights that are not possible
when working in isolation. The IARC's central hypothesis is that aversion-resistant drinking arises through a
combination of inherited behavioral and neurobiological vulnerabilities, as well as progressive changes in
fronto-striatal neurotransmission in response to drinking history.  The objective of this next IARC cycle is to
therefore apply coordinated, multi-disciplinary efforts to understand the brain and behavioral mechanisms
through which aversion-resistant drinking arises. Using the IARC's selected animal lines, our specific aims
are to determine how aversion resistant drinking may arise through: (1) Changes in medial prefrontal glutamate
systems, (2) unique impulsive endophenotypic behaviors and associated differential functioning in medial
prefrontal cortex, (3) forms of cognitive inflexibility and alterations in glutamate receptors in the brain's dorsal
striatum, and (4) drinking history and genetic influences on the corticostriatal encoding of alcohol-paired cues.
Accompanying these preclinical animal studies will be (5) a novel translational paradigm in humans to
determine how aversion-resistant alcohol seeking behaviors relate to drinking history, alcohol use disorder
symptoms, and brain physiology. The IARC will also (6) provide a pilot mechanism to develop new
investigators and research directions, and support promising directions related to the IARC's research
components. Finally, the IARC will expand existing educational, implementation, and outreach for primary care
providers and the legal profession. The IARC will thus function in a coordinated way to integrate human and
animal research on how genetic risk, alcohol exposure, and endophenotypic behaviors contribute to the
important problem of compulsive drinking.

## Key facts

- **NIH application ID:** 10064065
- **Project number:** 5P60AA007611-34
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** DAVID A. KAREKEN
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,663,064
- **Award type:** 5
- **Project period:** 1989-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064065

## Citation

> US National Institutes of Health, RePORTER application 10064065, Center on Genetic Determinants of Alcohol Ingestion and Responses to Alcohol (5P60AA007611-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064065. Licensed CC0.

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