# Ethanol modulation of a NE-astrocyte-DA arousal pathway

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $517,248

## Abstract

Project Summary
Alcohol Use Disorder (AUD) is a highly prevalent public health problem for which there are few
effective treatments. Sleep disturbances are highly comorbid with AUD and contribute
significantly to disorder progression. Moreover, sleep disturbances can be more difficult to treat
in individuals with AUD. Thus a critical need is to understand the mechanisms by which alcohol
regulates sleep behavior. Alcohol is well known to reduce sleep latency, however this is
followed by increased sleep fragmentation and problems with insomnia in individuals with AUD.
Alcohol is well known to have sedative properties, and subsequent insomnia-related AUD
symptoms have been proposed to be due to tolerance related disruptions in sleep-related
setpoints. Recently, we uncovered a novel pathway by which norepinephrine engages wake-
active dopamine neurons in the ventral periaqueductal gray (vPAG) to produce arousal. We find
in preliminary data that ethanol engages the activation of this pathway, providing a novel
potential mechanism through which alcohol can paradoxically drive wake behavior. Thus in the
project we propose to explore the mechanisms through which acute and chronic ethanol
exposure regulate this vPAG signaling pathway, and to explore the participation of this pathway
in acute and chronic alcohol-dependent alterations in sleep-related behaviors.

## Key facts

- **NIH application ID:** 10773848
- **Project number:** 1R01AA031269-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Danny G. Winder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $517,248
- **Award type:** 1
- **Project period:** 2024-07-08 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773848

## Citation

> US National Institutes of Health, RePORTER application 10773848, Ethanol modulation of a NE-astrocyte-DA arousal pathway (1R01AA031269-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10773848. Licensed CC0.

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