Role of the pre‐Bötzinger Complex in opioid‐induced respiratory depression in adult rats in‐vivo
Bibliographic record
Abstract
Respiratory rhythm is generated by pre‐Bötzinger Complex (PBC) neurons in‐vitro, with destruction of PBC neurons producing ataxic breathing in‐vivo. Activation of µ‐opioid receptors at the PBC decreases respiratory rate in neonatal rats in‐vitro, but the role of the PBC in opioid‐induced respiratory depression has not been tested in‐vivo. We recorded diaphragm and genioglossus (GG) muscle activities in adult rats with drugs applied to the PBC region by microdialysis probes. In anesthetized rats (n=6), application of the µ‐opioid receptor agonist fentanyl (100 µM) to the PBC decreased respiratory rate (mean = 43%, p=0.004 ) and GG activity (mean = 61%, p=0.007 ), with this depression reversed by the antagonist naloxone (100 µM). The time delay for fentanyl‐induced respiratory depression was correlated with the distance of the probe site from the PBC (r 2 = 0.83). Preliminary data in 2 freely behaving rats showed that fentanyl (150 µM) at the PBC also reduced respiratory rate in non‐REM sleep (~30%) but not wakefulness (~3%). The respiratory rate depression produced by fentanyl at the PBC also occurred with subcutaneous fentanyl (0.02‐0.1 mg/kg) in anesthetized and freely behaving rats (mean decreases 30‐54%, p<0.05 ). These data show that opioid‐sensitive neurons in the PBC mediate suppression of respiratory rate in‐vivo, with responses to µ‐opioid receptor agonists being prominent in non‐REM sleep and anesthesia.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".