Evaluating the reinforcing properties of oxycodone and oxymorphone using intravenous drug self-administration in male rats
Bibliographic record
Abstract
Oxycodone, a commonly abused opioid, and its metabolite oxymorphone are agonists at the μ-opioid receptor. While oxymorphone is more potent, and clinical data suggests a greater abuse liability, there is little data comparing them in preclinical models. We examined their reinforcing properties using the intravenous (IV) self-administration method. Male Wistar Han rats were implanted with IV catheters and trained to lever press for infusions of oxycodone and oxymorphone. Dose response curves were assessed using fixed ratio (FR) 1, FR3, FR5 and progressive ratio (PR) schedules. Responding was then extinguished and drug priming-induced reinstatement, a model of relapse, was assessed. Microdialysis was used to assess central concentrations of oxymorphone following IV oxycodone. Under FR1 schedules, in both oxycodone and oxymorphone self-administering rats, active lever pressing and infusions earned decreased with increasing dose, while intake increased, however the shape of the dose response curves differed. Oxymorphone, compared to oxycodone, exhibited a leftward shift in the dose-response curve, indicative of higher potency, but also a shallower slope and lower maximal active lever pressing and infusions. On the PR schedule, the highest breakpoint was observed for oxymorphone. Oxycodone (0.25 mg/kg) induced significant drug-priming reinstatement after extinction, while an equipotent dose of oxymorphone (0.025 mg/kg) approached significant reinstatement. After a bolus IV injection of oxycodone, oxymorphone was present in the cerebrospinal fluid at approximately 1/250th the concentration of oxycodone. These findings highlight distinct self-administration patterns between oxycodone, which is metabolized to oxymorphone in vivo, and oxymorphone itself, suggesting differences beyond potency at the μ-opioid receptor.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".