The opioid receptor antagonist naloxonazine uncovers the pronounced ventilatory stimulant effects of fentanyl in freely-moving rats
Bibliographic record
Abstract
We previously reported that administration of an opioid receptor antagonist elicits pronounced increases in minute ventilation in rats where the respiratory effects of formerly administered fentanyl had resolved. Thus, fentanyl induces the activation of an opioid receptor-dependent inhibitory system and a non-opioid receptor-dependent excitatory system - two systems with on-going counter-balancing effects on breathing. The objective of the present study was to determine whether administration of the potent, centrally-acting opioid receptor antagonist, naloxonazine (NLZ), during fentanyl-induced suppression of respiration, elicits an overshoot of breathing - above baseline values - suggesting the presence of an on-going excitatory ventilatory control system. The intravenous administration of 25, 50 or 75 μg/kg doses of fentanyl to separate groups of male Sprague Dawley rats elicited pronounced dose-dependent reductions in frequency of breathing, tidal volume, and minute ventilation. NLZ (1.5 mg/kg, IV) given 5 min after the injection of 25, 50 or 75 μg/kg doses of fentanyl - the timepoint in which the ventilatory depressant effects of fentanyl were most pronounced - elicited overshoots in frequency of breathing, tidal volume, and minute ventilation, as well as many other parameters, including, peak inspiratory and expiratory flows and inspiratory and expiratory drives. This overshoot in breathing, which lasted for 20-30 min, was associated with minor increases in the non-eupneic breathing index (NEBI), suggesting that the responses were not accompanied by unwanted effects on respiratory timing and mechanics. Understanding the mechanism(s) by which this non-opioid receptor-dependent excitatory ventilatory system acts may lead to the development of novel ventilatory stimulants.
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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".