Genetic deletion of mu opioid receptors from Kölliker‐Fuse neurons reduces morphine‐induced respiratory depression
Bibliographic record
Abstract
Activation of mu opioid receptors in the pontine Kölliker‐Fuse (KF) causes a reduction in respiratory rate in anesthetized rats. We have previously shown that mu opioid agonists hyperpolarize a population of KF neurons (Levitt et al., J Physiol , 2015). The goal of these experiments was to determine the contribution of the opioid‐sensitive KF neurons to the reduction in respiratory rate caused by systemic administration of the opioid agonist morphine. Targeted deletion of mu opioid receptors was accomplished by viral expression of Cre recombinase in the KF of mice with floxed mu opioid receptors. Experiments were performed 4– 6 weeks later. In whole‐cell recordings from brain slices, infected KF neurons were no longer hyperpolarized by opioid agonist, confirming deletion of mu opioid receptors. Head‐out plethysmography was used to measure respiratory rate. Morphine (10 mg/kg, ip) caused a significantly smaller reduction in respiratory rate in mice with bilateral deletion of mu opioid receptors from KF, compared to uninjected or GFP injected controls. The time‐course for the effect of morphine was also delayed in mice lacking mu receptors in KF neurons. Thus, opioid‐sensitive KF neurons contribute to, but are not entirely responsible for, systemic morphine‐induced respiratory depression. Support or Funding Information NIH K99/R00 DA038069
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".