# Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys

> **NIH NIH P50** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $382,414

## Abstract

PROJECT SUMMARY
Alcohol use disorder (AUD) persists as a costly public health problem that lacks widely effective medications
and strategies for prevention. The overarching scientific premise of this Project, like the others of the Wake
Forest Translational Alcohol Research Center (WF-TARC), is that the neural substrates that contribute to
vulnerability and resilience to AUD are not fully understood. Studies using nonhuman primate (NHP) subjects
have specific advantages that make them a critical part of a comprehensive, translational approach to
addressing this topic, including the possibility of experimental control not possible in human subjects and a
greater similarity to humans' neurobiology compared to rodents. Group-housed monkeys form linear social
hierarchies; social rank has been shown to influence sensitivity to abuse drugs, with subordinates showing
vulnerability to the abuse-related effects of stimulants and ethanol (EtOH). Project 2 of the WF-TARC will
exploit this differential sensitivity across social ranks to determine the behavioral and brain mechanisms that
underlie vulnerability to develop AUD. Behavioral studies will characterize rank-related differences in induction
of EtOH drinking, EtOH consumption over one year of 22 hours-per-day access and EtOH seeking behavior
during abstinence using an extremely well-characterized NHP EtOH self-administration model of long-term
drinking in humans. We will also determine whether dominant and subordinate monkeys differ in sensitivity to
chronic treatment potential medications for AUD. In parallel to these experiments, brain imaging studies using
magnetic resonance imaging will characterize the structural and functional differences between dominants and
subordinates, and determine the specific changes that occur in grey and white matter integrity, cerebral blood
flow and functional connectivity during long-term EtOH drinking and subsequent abstinence. Importantly, these
NHP studies occupy a critical position in the translational structure of the WF-TARC, supporting forward and
backwards translation to inform and extend findings in rodent and human projects. NHP imaging studies will
focus on the same brain regions and nodes that will be imaged in human subjects and studied and
manipulated in rodents. Secondary analyses on imaging data will expand this focus to the entire brain. Taken
together, the results of the studies in this Project, particularly in combination with data generated in other
components of the WF-TARC, will provide a comprehensive account of brain differences between populations
that are resistant versus vulnerable to AUD. This knowledge will ultimately help practitioners direct preventive
efforts to groups who will most benefit from them, and will identify new targets for more effective medications
targeted to the most vulnerable populations.

## Key facts

- **NIH application ID:** 10079837
- **Project number:** 5P50AA026117-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Paul W. Czoty
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,414
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079837

## Citation

> US National Institutes of Health, RePORTER application 10079837, Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys (5P50AA026117-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10079837. Licensed CC0.

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