Effect of neonatal maternal separation on inspiratory response to hypercapnia in male rats: implication of central and peripheral chemodetections

Abstract

Neonatal maternal separation (NMS) is a clinically relevant stress model which disrupts respiratory control development. NMS reduces the ventilatory response to CO2 in rats but the underlying mechanisms are unknown. The present study aimed to determine whether attenuation of this hypercapnic response occurs at the central or peripheral level. Pups subjected to NMS were separated from their mother 3h/day from post natal days 3 to 12. Fictive ventilation was measured during normocapnia and hypercapnia (PaCO2: 10Torr above baseline) using 2 approaches on anaesthetized (urethane 1g/kg + isoflurane 0.5%) adult male rats. First, to test the central chemosensibility, we recorded phrenic nerve activity in vagotomized, paralyzed and ventilated (FiO2: 0.5) rats. No differences were observed between groups. We then tested the implication of peripheral chemodetection in non‐vagotomized and spontaneously breathing rats using bilateral chemodenervation. Recording of diaphragmatic EMG showed a decreased of baseline breathing frequency by 35% in control rats only. During hypercapnia, breathing frequency decreased by 31% in controls but increased by 15% in NMS. This opposite response eliminates the difference between groups in minute activity responses. These results show that disruption of carotid body function (and/or central integration) contributes to the phenotype observed in NMS rats. Supported by CIHR.