Early life stress and hormonal status influence orexin‐1 receptor expression in structures regulating cardiorespiratory responses to CO<sub>2</sub>
Bibliographic record
Abstract
Abstract Excessive cardiorespiratory responses to CO2 are a hallmark of panic disorder (PD). Female sex and exposure to early life stress are risk factors for PD. Neonatal maternal separation (NMS; 3 h/day, postnatal days 3–12) augments the ventilatory response to CO2 by ∼35% relative to controls; this effect is most notable during pro‐oestrus but is not observed in males. Orexin‐1 receptor (OX1‐R) antagonism attenuates the CO2 response of NMS females. In the limbic system, stress and ovarian hormones influence OX1‐R expression, but the impact of these factors on OX1‐Rs in regions regulating the cardiorespiratory responses to CO2 is unknown. Here, we hypothesised that ovarian hormones and NMS determine OX1‐R expression in structures regulating the CO2 response; we used in situ hybridisation to quantify OX‐1R mRNA expression in the brains of adult NMS and control rats. Brains were harvested from females that were either in pro‐oestrus (high ovarian hormones) or 2 weeks post ovariectomy (OVX; low ovarian hormones); males were included for comparison. Hormonal status influenced the intensity of the OX1‐R signal in the medial amygdala, raphe obscurus (RObs) and the A5 area, but the direction of the changes (increase vs. decrease) was structure‐specific. Significant NMS × hormonal status interactions were noted in the dorsal raphe, the locus coeruleus, the nucleus of the solitary tract and the A5 area; the effects were structure‐specific. As the dorsal raphe was the only structure in which the changes in OX1‐R expression matched the sex‐specific effect of NMS on the CO2 response, this structure likely contributes to respiratory manifestations of PD.
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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 | 0.000 |
| 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".