Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats

Abstract

The respiratory network undergoes significant development during the postnatal phase, including the maturation of the catecholaminergic (CA) system. However, postnatal development of this network and its effect on the control of pulmonary ventilation (V̇_E), is not fully understood. We investigated the involvement of brainstem CA neurones in respiratory control during postnatal (P) development (P7-8, P14-15 and P20-21), in male and female rats, through chemical injury with conjugated saporin anti-dopamine beta-hydroxylase (DβH-SAP). Thus, DβH-SAP (420 ng μL⁻¹), saporin (SAP) or phosphate buffered solution (PBS) was injected into the 4th ventricle of neonatal Wistar rats of both sexes. V̇_E and oxygen consumption were recorded one week after the injections in unanaesthetized neonatal and juvenile rats during room air and hypercapnia. The resting ventilation was higher in both male and female P7-8 lesioned rats by 33%, and a decrease in respiratory variability was observed in males. The hypercapnic ventilatory response (HCVR) was altered in male and female lesioned rats at all postnatal ages. At P7-8, the HCVR for males and females was increased by 37% and 30%, respectively. For both sexes at P14-15 rats, the increase in V̇_E during hypercapnia was 37% higher for lesioned rats. A sex-specific difference in HCRV was observed at P20-21, with lesioned males showing a 33% decrease, and lesioned females showing an increase of 33%. We conclude that brainstem CA neurones exert a tonic inhibitory effect on V̇_E in the early postnatal days of a rat's life, increase variability in P7-8 males and modulate HCRV during the postnatal phase.

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