Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats
Bibliographic record
Abstract
Caffeine is widely used to treat apneas of prematurity during the neonatal period; however, the potential consequences of administering a neonatal caffeine treatment (NCT) during a critical period for respiratory control development are unknown. The present study therefore determined whether NCT in rats alters the hypoxic respiratory chemoreflex measured at adulthood. Newborn rats received either caffeine (15 mg/kg) or water (control) each day from postnatal day 3 to 12. The ventilatory response to a hypoxic challenge (inspired O(2) fraction = 0.12) was first evaluated in awake adult female and male rats using whole body plethysmography. Results showed that NCT increased the initial phase of the breathing frequency response to hypoxia in males only. This result was confirmed in anesthetized and artificially ventilated adult male rats where NCT also increased the phrenic burst frequency response to hypoxia. RT-PCR assessment of mRNA encoding for adenosine A(1A) and A(2A) receptors, dopamine D(2) receptors, and tyrosine hydroxylase in the rat carotid bodies showed that NCT enhanced mRNA expression levels of adenosine A(2A), dopamine D(2) receptors, and tyrosine hydroxylase of males but not females. Subsequent experiments on awake male rats showed that injection of the adenosine A(2A) receptor antagonist ZM2413855 (1 mg/kg ip) before ventilatory measurements abolished, in NCT rats, the enhanced respiratory frequency response observed during the early phase of hypoxia. We propose that NCT elicits a sex-specific increase in the hypoxic respiratory chemoreflex, which is related, at least partially, to an enhancement in adenosine A(2A) receptors in the rat carotid body.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".