Orexin 1 Receptors Are necessary for Phase‐Specific Enhancement of The Hypercapnic Ventilatory Response in Female Rats Subjected to Neonatal Stress
Bibliographic record
Abstract
Panic disorder (PD) is an anxiety disorder that affects ~3 times more women than men. Respiratory manifestations of PD appear after puberty and include an increased sensitivity to CO 2 . This observation suggests that ovarian function contributes to the onset of PD. In humans and rodents, exposure to stress during early life alters brain development and is considerate a risk factor for PD. Using Neonatal Maternal Separation (NMS) as a stressor, we showed that NMS augments the ventilatory response to CO 2 in adult female rats but these effects are not present in pre‐pubertal rats. Based on these observations we first tested the hypothesis that cyclic hormone fluctuations influence chemosensitivity. In addition to their involvement in fear and vigilance responses, orexin neurons (ORX) are CO 2 sensitive. Based on these properties, ORX has been linked to PD. Thus, we also tested the hypothesis that ORX receptors are necessary for stress‐related enhancement of the CO 2 response. Pups subjected to NMS were placed in an incubator for 3 h/day from postnatal day 3 to 12. Control pups remained undisturbed. Female rats were reared until adulthood (P60–70), and the ventilatory response to CO 2 was measured by whole‐body plethysmography (FICO 2 = 0.05, for 10 min). OX 1 antagonist (SB334867; 15mg/kg) or vehicle (ip) was injected 45 to 60 minutes before start the recordings. After the experiment, the oestrus cycle was verified by vaginal smear. In controls, the ventilatory response to CO 2 did not change across the estrus cycle. The hypercapnic ventilatory response of NMS females was phase‐dependent with the greatest responsiveness observed during proestrus. Pharmacological inactivation of OX 1 receptors had not effect on the hypercapnic response of controls, but reduces the respiratory response to CO 2 in NMS females, the most important effects were observed during proestrus and metaestrus phases. Based on the phase‐dependent increase in NMS females, we conclude that stress interferes with the influence that sex‐hormones exert on respiratory control. These effects may take place in the hypothalamic region that contain ORX neurons since activation of OX 1 receptors are necessary for stress‐related enhancement of the hypercapnic ventilatory response. These results provide new insight into the pathophysiology of PD. Support or Funding Information Canadian Institutes of Health Research and CNPq ‐ Brazil.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".