# Mechanistic studies of opiate withdrawal-induced sleep disturbances

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $414,450

## Abstract

PROJECT SUMMARY
 The majority of patients with Opioid Use Disorder (OUD) report sleep problems such as insomnia. Sleep
disruption commonly occurs during opiate withdrawal and has been considered as a major factor that contributes
to relapse. However, little is known about the underlying mechanisms, and the circuits/neurons/genes that are
involved. One of major component of both the opioid withdrawal and arousal circuitry resides in the
monoaminergic nuclei—the locus coeruleus (LC), which is known to abundantly express µ-opioid receptors,
mediates opioid withdrawal symptoms, and promote wakefulness. In the proposed project, we will combine
activity-dependent labelling and intersectional strategies to specifically target the wake-active populations of LC
noradrenergic (LCNE-Wake) neurons and determine whether they are critical for morphine withdrawal-induced
sleep disturbances. In Aim 1, using cutting-edge systems neuroscience tools, we will determine whether
spontaneous withdrawal from chronic morphine administration disrupts the neuronal activity and membrane
properties of LCNE-Wake neurons, and functionally and molecularly characterize these dysfunctional neurons. In
Aim 2, we will further evaluate the functional role of major presynaptic inputs of LC, gigantocellular reticular
nucleus (Gi) of medulla in withdrawal-induced sleep disturbances, test whether activation of GABAergic neurons
in Gi can sufficiently mitigate the dysregulated sleep, and lastly map the spatial transcriptomic signatures of
Gi-LC neurobiological pathway during morphine withdrawal. Successful completion of these aims will advance
our understanding of the circuit mechanisms underlying OUD-associated sleep disturbances, potentially leading
to the development of effective therapies.

## Key facts

- **NIH application ID:** 10985838
- **Project number:** 1R01DA061306-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Peng Zhong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $414,450
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985838

## Citation

> US National Institutes of Health, RePORTER application 10985838, Mechanistic studies of opiate withdrawal-induced sleep disturbances (1R01DA061306-01). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10985838. Licensed CC0.

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