Neonatal stress increases respiratory instability in rat pups

Neonatal maternal separation (NMS) is a form of stress that has persistent, sex-specific effects on respiratory control development. In adult male (but not female) rats, NMS increases the hypoxic ventilatory response and augments respiratory instability during sleep; however, the effects of NMS on respiratory control prior to puberty are unknown. This study tested the hypothesis that NMS augments respiratory instability and the O2 chemosensitivity in 12 days old rats. Pups subjected to NMS were placed in an incubator 3 h/day from P3 to P12. Controls were undisturbed. Breathing and apnea index were measured in normoxia with plethysmography. The ventilatory chemoreflex was assessed by measuring the increase in breathing frequency upon brief exposure to a hypoxic challenge (FIO2=0.09FIO2=0.09; 5 min). In normoxia, NMS augments the coefficient of variation (CV; an index of respiratory instability) of respiratory frequency and the number of apneas; this effect was more pronounced in male pups. We conclude that disruption of respiratory regulation by NMS is already apparent at P12. Based on results showing that plasma corticosterone levels of NMS pups were still elevated one day after the last NMS episode and the lack of effect of NMS on the O2 chemoreflex index, we propose that disruption of hypothalamic regulation contributes to respiratory instability in NMS pups.