The Role of the Estrous Cycle on Human CYP2D6-mediated Harmine Response in CYP2D6-transgenic Mice
Bibliographic record
Abstract
CYP2D is a drug metabolising enzyme found in the brain and the liver, whose activity in brain is influenced by both genetics and environment. Our aim was to investigate whether drug metabolism by CYP2D6 in brain could be altered by the estrous cycle. Using a previously established method, CYP2D6-transgenic and wild type female mice were given an intracerebroventricular injection of an inhibitor. After 24 hours, there may be irreversible inhibition of human CYP2D6 in transgenic brain, but not liver, and no irreversible inhibition of mouse CYP2D in either brain or liver. Harmine-induced hypothermia was increased in transgenic females in estrus but not diestrus, suggesting more CYP2D6 in brain in estrus. There was no effect of this inhibitor pre-treatment on harmine response in wild type females, or on peripheral drug concentrations. These data provide support that the menstrual cycle may impact CYP2D6 in human brain sufficiently to change drug response.
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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) | 0.004 | 0.001 |
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".