# Perinatal opioids impair maturation of vital respiratory networks

> **NIH NIH R21** · UNIVERSITY OF OREGON · 2022 · $174,581

## Abstract

PROJECT SUMMARY
The number of infants born with Neonatal Abstinence Syndrome (NAS) after maternal opioid exposure is
dramatically rising, yet the direct effects of perinatal (maternal + neonatal) opioids on the maturation of neural
networks is not well-characterized. Infants diagnosed with NAS exhibit diverse negative outcomes, including
respiratory complications that remain poorly understood. Clinically, these infants are treated with exogenous
neonatal opioids to curb the withdrawal symptoms, but there is no accepted standard clinical dosing regime and
the long-term effects of neonatal opioids treatment remain unclear. The objective of this proposal is to
understand the direct effects of maternal and neonatal opioid exposure on the maturation and refinement
of vital respiratory control networks maintaining breathing. This project will utilize a novel animal model
to inform the development of a clinical standard of care to treat NAS. Unlike other animal models delivering
maternal opioids from conception, the proposed model delivers opioids at the onset of respiratory network activity
in utero to target the direct effects of opioids on network maturation. Two specific hypotheses will be tested: 1)
Maternal opioids cause instability in neonatal breathing by disrupting reciprocal communication between two
respiratory networks; 2) Acute, exogenous opioids in neonates after maternal opioids promote pathological
maturation of respiratory networks, potentiating neonatal breathing impairments and blunting the response to
acute opioids. Our recently published work using this model showed increased apneas (pauses in breathing)
and impaired chemoreflexes (responses to respiratory stimuli) in neonates after perinatal opioids. Further, our
preliminary data suggest treating NAS infants with acute opioids increase apneic episodes over time, highlighting
windows of increased vulnerability for respiratory failure. Our data begin to localize the source of breathing
deficits after perinatal opioids, which we hypothesize include impaired maturation of the preBötzinger Complex
(fundamental neural network controlling breathing and highly opioid-sensitive) and impaired communication
between the preBötzinger Complex and parafacial respiratory group (a second, opioid-insensitive respiratory
network), independent of pontine networks. Such insights into mechanisms of impaired breathing in NAS infants
are only possible with an innovative, multidisciplinary approach in a rodent model. Our experimental approaches
include: in vivo plethysmography assessment of breathing, in vitro neurophysiology allowing direct access to the
isolated neural networks controlling breathing, and identification of opioid receptors in respiratory control regions
using immunohistochemistry. Results from the proposed studies will significantly advance our understanding of
the mechanisms by which perinatal opioids impair maturation of respiratory control networks. These basic
science studies are vita...

## Key facts

- **NIH application ID:** 10449914
- **Project number:** 1R21DA054295-01A1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Adrianne Genest Huxtable
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $174,581
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449914

## Citation

> US National Institutes of Health, RePORTER application 10449914, Perinatal opioids impair maturation of vital respiratory networks (1R21DA054295-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449914. Licensed CC0.

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