Enhancement of the hypoxic ventilatory response following neonatal maternal separation: the role of testosterone in adult male rats

Abstract

Neonatal maternal separation (NMS) disrupts normal neurological development in mammals. The hypoxic ventilatory response (HVR) of adult male rats previously subjected to NMS is ~25% greater than controls while the response of NMS females is reduced by ~30% (Genest et al., 2004). To address the role of sexual hormones on the respiratory phenotype observed in NMS males, we compared the HVR of normal adults (10‐14 weeks old; controls n = 6, NMS n = 6) with that of gonadectomised (GDX) adult males (controls n = 7, NMS n = 6) in which circulating testosterone levels are considerably reduced. Pups subjected to NMS were placed in an incubator 3h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. Rats were then reared until adulthood when HVR was measured with plethysmography (12% O2, 20 min). In controls, GDX had no effect on the HVR. In NMS rats, GDX reduced the HVR 50% below that of controls (GDX x NMS; p = 0.03) with a pattern now similar to the respiratory phenotype of female rats. These results indicate that testosterone is necessary for full expression of the HVR in NMS but not in control males, and likely contributes to the enhancement of the HVR following NMS. Supported by the CIHR.