Social defeat stress switches the neural system mediating benzodiazepine conditioned motivation.
Bibliographic record
Abstract
Benzodiazepines have been demonstrated to have a high abuse liability in persons suffering from anxiety but have demonstrated mixed abuse liability findings in preclinical models. We hypothesized that by modeling anxiety in a male C57BL/6 mouse model it would be possible to reveal a preference for benzodiazepines within this subpopulation through negative reinforcement. Using the Tube Test of Social Dominance and the Resident/Intruder Paradigm we investigated whether animals identified as dominant or submissive/defeated would differentially display a preference for midazolam (a short acting benzodiazepine) in a conditioned place preference paradigm. Consistent with our hypotheses, benzodiazepine conditioned motivation was mediated by negative reinforcement as submissive but not dominant mice displayed a preference for midazolam. Furthermore, different neural systems mediated midazolam conditioned motivation depending on the stress status of the animal (single vs. repeated stress-as induced by the Resident/Intruder Paradigm). Singly stressed animals showed midazolam place preferences through a dopamine-independent pathway, whereas the place preferences of repeatedly stressed animals were mediated through a dopamine-dependent pathway. This demonstrates that stress is sufficient for switching the neural system mediating midazolam conditioned motivation. Finally, midazolam reinforcement in the conditioned place preference paradigm was shown to be predictive for dominance/submission status.
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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 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".