Neonatal Maternal Separation Disrupts Regulation of Sleep and Breathing in Adult Male Rats

Abstract

Neonatal maternal separation (NMS) disrupts development of cardiorespiratory regulation. Adult male rats previously subjected to NMS are hypertensive and show a hypoxic ventilatory response greater than that of controls. These results have been obtained in awake or anesthetised animals, and the consequences of NMS on respiratory control during normal sleep are unknown. This study tested the following. NMS augments respiratory variability across sleep-wake states, and NMS-related enhancement of the hypoxic ventilatory response occurs during sleep. Two groups of adult rats were used: controls (no treatment) and rats subjected to NMS. Ventilatory activity, coefficient of variation, and hypoxic ventilatory response were compared between groups and across sleep-wake states. Male Sprague Dawley rats-NMS: n=11; controls: n=10. Pups subjected to NMS were isolated from their mother for 3 hours per day from postnatal days 3 to 12. Controls were undisturbed. At adulthood, sleep-wake states were monitored by telemetry, and ventilatory activity was measured using whole-body plethysmography. Sleep and breathing were measured for 2.5 hours (in the morning) while the rats were breathing room air. Data were analysed in 20-second epochs. Rats were then exposed to a brief (90-sec) hypoxic episode (nadir = 12% O2) to measure the hypoxic ventilatory response. The coefficient of variability for tidal volume and breathing frequency decreased during sleep but remained more elevated in NMS rats than in controls. During non-rapid eye movement sleep, the breathing-frequency response to hypoxia of NMS rats was significantly greater than that of controls. Neonatal maternal separation results in persistent disruption of respiratory control during sleep.