Determining the opioid sensitivity of projections from the Kölliker‐Fuse to respiratory rhythm generators

Abstract

Opioid‐induced respiratory suppression is the primary cause of death in individuals who overdose on opioids, but the mechanism remains elusive. Mu opioid receptor agonists have been shown to hyperpolarize a population of neurons in the Kölliker‐Fuse nucleus (KF) due to activation of G protein‐mediated inwardly rectifying (GIRK) conductance (Levitt et al., J Physiol, 2015). The KF, required for normal eupneic breathing, adjusts respiratory rhythm and rate by modulating respiratory rhythm generators. Given the interconnectivity of the KF and respiratory rhythm generators, we hypothesize that KF neurons projecting to respiratory rhythm generators are opioid‐sensitive and thus a possible mechanism by which opioids reduce respiratory rate. The goal of these experiments was to determine if opioid‐sensitive KF neurons project to respiratory rhythm generators. Fluorescent beads (FluoSpheres 580/605, ThermoFisher) were injected into respiratory rhythm generators, including pre‐Bötzinger complex (preBötC) and post‐inspiratory complex (PiCo), of mice. Whole‐cell voltage‐clamp recordings were made from retrograde‐labeled neurons in the KF. Mu opioid receptor‐mediated outward currents were identified in KF neurons that project to the preBötC. Therefore, opioid‐sensitive connections between the KF and respiratory rhythm generators may be involved in opioid‐induced respiratory suppression.Support or Funding InformationSupported by NIH grant DA038069.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.