# 4/8: INIA Stress and Chronic Alcohol Interactions: Impact of stress mediated locus coeruleus dysregulation on cognitive control and excessive drinking

> **NIH NIH U01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $319,000

## Abstract

PROJECT SUMMARY/ABSTRACT
There is strong comorbidity between alcohol use disorders and chronic stress and anxiety. Dysfunction within
overlapping neural targets of alcohol and stress may facilitate the development of this comorbid phenotype.
The locus coeruleus norepinephrine (LC-NE) system is sensitive to both alcohol and stress and plays an
important role in cognitive and emotional regulation of behavior. Plasticity within LC-NE circuits after chronic
stress and alcohol can produce feed-forward effects, elevating stress and anxiety via the HPA axis and
decreasing cognitive control by disrupting prefrontal cortex (PFC) function. The consequence of this stress-
cognition “double-hit” is an increased need to drink and a decreased control over drinking. Our preliminary
evidence demonstrates that chronic intermittent ethanol exposure in addition to repeated swim stress, disrupts
PFC dependent cognition and increases excessive drinking more than either ethanol or stress alone. In these
studies we will investigate the LC as a key target of stress/ethanol maladaptations and the potential for LC-NE
targeted therapeutics to ameliorate stress/ethanol induced executive dysfunction, elevated anxiety, and
excessive drinking. This project will provide new insights into the role of LC-NE dysfunction after chronic stress
and alcohol. Our results will identify novel circuit changes underlying excessive alcohol consumption and the
potential for NE targeted therapies in treating cognitive and emotional dysfunction in alcohol use disorders.

## Key facts

- **NIH application ID:** 10109092
- **Project number:** 5U01AA025481-05
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** DAVID E MOORMAN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,000
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109092

## Citation

> US National Institutes of Health, RePORTER application 10109092, 4/8: INIA Stress and Chronic Alcohol Interactions: Impact of stress mediated locus coeruleus dysregulation on cognitive control and excessive drinking (5U01AA025481-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10109092. Licensed CC0.

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