# Influence of Opioids on the Brainstem Respiratory Network

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $681,622

## Abstract

PROJECT SUMMARY
Many of the 54,000 opioid-related deaths in 2017 were due to respiratory depression. The specific
mechanisms by which opioids depress breathing are not fully understood. Current hypotheses focus on single
areas within the respiratory network, such as the pons or pre-Bötzinger complex. However, perturbation of
these areas has not fully predicted the actions of opioids to depress breathing. Based on preliminary data and
model simulations we have developed the following hypothesis: opioid administration induces
reconfiguration of the respiratory network in a dose-dependent manner. This reconfiguration involves
alterations in the pattern of discharge of some neurons (discharge identity), loss of synchrony among
interconnected inspiratory neuron networks in the ventral respiratory column (VRC) and altered
functional connectivity within and between respiratory areas in the brainstem. This project has three
Specific Aims: 1) Determine the influence of opioids on functional network interactions between neurons in
the nucleus tractus solitarius (NTS), raphe, pontine, and VRC that regulate motor output to respiratory
muscles, 2) Determine the role of opioids in modulating synchrony within inspiratory neuron circuits in the
VRC, 3) Generate a network-scale model of the brainstem circuits that control breathing in the presence of
opioids. We anticipate this project will lead to: a) identification of elements of the respiratory control network
that participate in opioid-mediated reconfiguration, b) delineation of functional relationships between E-T/NBM
in the pons, raphe, NTS area and VRC neurons that contribute to depression of breathing by opioids, c) the
role of impaired synchrony in inspiratory neuron networks in reduced motor drive produced by opioids, and d)
new predictive model will be produced featuring the network-scale mechanisms that contribute to opioid
depression of breathing. This new knowledge will provide a critical step in understanding the network scale
mechanisms of action of opioids to depress breathing.

## Key facts

- **NIH application ID:** 10322091
- **Project number:** 5R01HL155721-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** DONALD C BOLSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $681,622
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322091

## Citation

> US National Institutes of Health, RePORTER application 10322091, Influence of Opioids on the Brainstem Respiratory Network (5R01HL155721-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322091. Licensed CC0.

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