Early life stress and hormonal status influence orexin‐1 receptor expression in structures regulating cardiorespiratory responses to CO2
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; t...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
|
| Series: | Experimental Physiology |
| Subjects: | |
| Online Access: | https://doi.org/10.1113/EP092431 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 0958-0670 1469-445X |