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

> **NIH NIH P60** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $1,756,278

## Abstract

Project Summary/Abstract: Overall Indiana Alcohol Research Center (IARC)
 The Indiana Alcohol Research Center (IARC) has devoted more than three decades to understanding
alcohol use disorder (AUD) risk using neuroscientific and behavioral genetic tools. This prior work leads us to
study the heritable, neurobiological, and behavioral factors that drive binge and high-intensity drinking (BHID).
Most research on BHID focuses on harm from numbers of drinks or level of alcohol exposure but does not
account for “front-loading”— the initial rapid drinking to ostensibly enhance alcohol’s rate of change in the brain
and its resulting effects. Although such drinking is initially more intoxicating, compensatory (neuro-)
adaptations can create an acute tolerance to rewarding effects, which in turn induces a need to increase
consumption. Judgments about the next drink can then be affected so as to sustain intake, pushing alcohol
exposure into high-intensity levels. The long-term goal of the IARC is to deploy its multidisciplinary efforts to
understand the heritable origins of responses to alcohol and development of AUD. The objective of this next
IARC cycle is to study brain circuits and behaviors that influence both the rapid front-loading and sustained
drinking behaviors that elevate alcohol concentration to hazardous, high-intensity levels. In studies of both
humans and our selected, alcohol-preferring animals, our specific aims will be to: (1) Study human neural,
perceptual, and subject factors that relate to: a) preferences for a steeper rise in alcohol concentration and b)
acute tolerance to a sustained binge-level exposure; (2) Study heritable differences in the structure and
function of frontal brain circuitry hypothesized to underlie front-loading, high drinking, and behavioral inhibition
in rat lines selected for high alcohol intake; (3) Study heritable differences in insula circuits hypothesized to
mediate front-loading and subsequent sustained high drinking in rat lines selected for high alcohol intake, as
well as potential related contributors to high intensity drinking; and (4) Study how adaptation in glutamatergic
input to the dorsomedial striatum from basolateral amygdala and insula contributes to alcohol tolerance, driving
a) sustained high-intensity drinking in the high-consuming cHAP mouse line, and b) binge-like drinking in the
C56BL/6J inbred mouse strain. These projects are supported by service cores to (5) provide selected lines of
alcohol-preferring and animals and (6) conduct higher-level network-analyses and computational modeling of
results from the research components. (7) A Pilot Core assists new investigators to alcohol research and
explores new ideas, while (8) an Information and Dissemination Core educates and advises the community,
schools, healthcare providers, and state policy makers about both BHID and AUD. The IARC thus functions in
a coordinated way to integrate human and animal research, and to determine how heritable ri...

## Key facts

- **NIH application ID:** 10757889
- **Project number:** 5P60AA007611-37
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** DAVID A. KAREKEN
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,756,278
- **Award type:** 5
- **Project period:** 1989-12-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757889

## Citation

> US National Institutes of Health, RePORTER application 10757889, Center on Genetic Determinants of Alcohol Ingestion and Responses to Alcohol (5P60AA007611-37). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10757889. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*