Differential Effects of Morphine on a Dispersed Respiratory Network to Induce Respiratory Depression in Awake Mice
Bibliographic record
Abstract
Respiratory depression is the main cause of death from an opioid overdose. The reduction in respiratory rate is the result of activation of mu opioid receptors in respiratory centers, such as the pontine Kölliker‐Fuse nucleus and the medullary pre‐Bötzinger complex. The goal of this study was to directly compare the relative contribution of opioid‐sensitive neurons in the Kölliker‐Fuse nucleus and the pre‐Bötzinger complex to respiratory depression caused by systemic administration of the opioid agonist morphine in adult mice. We conditionally knocked out mu opioid receptors using virally mediated Cre expression in mice with floxed mu opioid receptors. Whole‐cell patch clamp recordings in acute brain slices showed that this approach successfully eliminates mu opioid receptor‐mediated outward currents from Kölliker‐Fuse nucleus neurons. Next, using plethysmography, we found that deletion of mu opioid receptors from either the Kölliker‐Fuse nucleus or pre‐Bötzinger complex attenuated the decrease in respiratory rate induced by an analgesic dose of morphine (10mg/kg). Administration of high doses of morphine (30mg/kg and 100mg/kg) resulted in reduced respiratory rates similar to that observed in control animals. Morphine administration also caused an increased level of irregularity in the breathing pattern with short intervals of fast and slow breathing and an increased number of apneas. These effects were dependent on the administered dose of morphine, as well as the location of mu opioid receptor removal. Our results indicate that multiple pontine and medullary respiratory groups differentially contribute to morphine‐induced respiratory depression, and none are entirely responsible for the effects of morphine. Support or Funding Information This work was supported by National Institutes of Health Grants DA038069 (E.S.L.) and DA05010 (B.L.K.). A.G.V. was funded by the UF Breathing Research and Therapeutics Training Program (T32 HL134621) and the Center for Respiratory Research and Rehabilitation. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".