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Female sex and exposure to early life stress are risk factors for PD. Neonatal maternal separation (NMS; 3\u00a0h\/day, postnatal days 3\u201312) augments the ventilatory response to CO<jats:sub>2<\/jats:sub> by \u223c35% relative to controls; this effect is most notable during pro\u2010oestrus but is not observed in males. Orexin\u20101 receptor (OX1\u2010R) antagonism attenuates the CO<jats:sub>2<\/jats:sub> response of NMS females. In the limbic system, stress and ovarian hormones influence OX1\u2010R expression, but the impact of these factors on OX1\u2010Rs in regions regulating the cardiorespiratory responses to CO<jats:sub>2<\/jats:sub> is unknown. Here, we hypothesised that ovarian hormones and NMS determine OX1\u2010R expression in structures regulating the CO<jats:sub>2<\/jats:sub> response; we used in situ hybridisation to quantify OX\u20101R mRNA expression in the brains of adult NMS and control rats. Brains were harvested from females that were either in pro\u2010oestrus (high ovarian hormones) or 2\u00a0weeks post ovariectomy (OVX; low ovarian hormones); males were included for comparison. Hormonal status influenced the intensity of the OX1\u2010R signal in the medial amygdala, raphe obscurus (RObs) and the A5 area, but the direction of the changes (increase vs. decrease) was structure\u2010specific. Significant NMS\u00a0\u00d7\u00a0hormonal 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\u2010specific. As the dorsal raphe was the only structure in which the changes in OX1\u2010R expression matched the sex\u2010specific effect of NMS on the CO<jats:sub>2<\/jats:sub> response, this structure likely contributes to respiratory manifestations of PD.<\/jats:p>","DOI":"10.1113\/ep092431","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:47:39Z","timestamp":1741744059000},"page":"1138-1153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Early life stress and hormonal status influence orexin\u20101 receptor expression in structures regulating cardiorespiratory responses to CO<sub>2<\/sub>"],"prefix":"10.1113","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-3047","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Fournier","sequence":"first","affiliation":[{"name":"Research Center of the Qu\u00e9bec Heart and Lung Institute Laval University  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