The utility of maraviroc, an antiretroviral agent used to treat HIV, as treatment for opioid abuse? Data from MRI and behavioural testing in rats
Bibliographic record
Abstract
BACKGROUND: Maraviroc is an antiretroviral agent and C-C chemokine coreceptor 5 (CCR5) antagonist that is currently used to treat human immunodeficiency virus. CCR5/μ-opioid receptor heterodimerization suggests that maraviroc could be a treatment for oxycodone abuse. We treated rats with maraviroc to explore its effect on oxycodone-seeking and its interference with the analgesic effects of oxycodone. We used resting-state blood-oxygen-level-dependent functional connectivity to assess the effect of maraviroc on oxycodone-enhanced coupling in the reward circuitry and performed behavioural tests to evaluate the effect of maraviroc on oxycodone rewarding properties and on oxycodone-seeking after prolonged abstinence. METHODS: Two groups of rats were exposed to 8 consecutive days of oxycodone-conditioned place preference training and treatment with maraviroc or vehicle. Two additional groups were trained to self-administer oxycodone for 10 days and then tested for drug seeking after 14 days of abstinence with or without daily maraviroc treatment. We tested the effects of maraviroc on oxycodone analgesia using a tail-flick assay. We analyzed resting-state functional connectivity data using a rat 3-dimensional MRI atlas of 171 brain areas. RESULTS: Maraviroc significantly decreased conditioned place preference and attenuated oxycodone-seeking behaviour after prolonged abstinence. The analgesic effect of oxycodone was maintained after maraviroc treatment. Oxycodone increased functional coupling with the accumbens, ventral pallidum and olfactory tubercles, but this was reduced with maraviroc treatment. LIMITATIONS: All experiments were performed in male rats only. CONCLUSION: Maraviroc treatment attenuated oxycodone-seeking in abstinent rats and reduced functional coupling in the reward circuitry. The analgesic effects of oxycodone were not affected by maraviroc.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".