Regulation of the hypothalamic-pituitary-adrenal axis in the neonatal rat: the role of maternal behavior.

There is a growing literature that indicates that exposure to elevated levels of glucocorticoids can result in long term consequences for the developing brain. In the developing rodent there is a period from about day 4-14 when the adrenal response to stress is either minimal or non-existent thus resulting in stable low levels of circulating glucocorticoids. This has been designated as the stress hypo-responsive period (SHRP). Numerous experiments have demonstrated that maternal factors are critical for the regulation of the pup's hypothalamic-pituitarty adrenal (HPA) axis and the maintenance of the SHRP. Following 24 h of maternal deprivation the neonatal rat shows elevated basal levels of corticosterone and exhibits a robust corticosterone and ACTH response to mild stress. Further c-fos mRNA in the paraventricular nucleus is enhanced following stress in deprived pups. At least three aspects of maternal behavior play a role in the regulation of the HPA axis during development. Tactile stimulation appears capable of inhibiting most of the brain-related changes that occur following maternal deprivation. Feeding is essential for maintaining the adrenal unresponsive and reduces the sensitivity of the adrenal to ACTH. Passive contact suppresses the response to stress. In the adult corticotropin-releasing hormone (CRH) is the major neuropeptide that controls pituitary ACTH secretion. In the maternally deprived pup CRH gene transcription is down regulated and arginine vasopressin (AVP) appears to assume the major regulatory hormone that modulates ACTH. These data all indicate that maternal factors are responsible for actively inhibiting the endocrine responses to stress postnatally. Further, maternal deprivation also results in increased cell death in several brain regions. Thus during development most of the peripheral and central stress responsive systems are capable of being activated. However, under conditions of normal dam-pup interactions these responses are mostly suppressed by the dam's behavioral interaction with the pups thus preventing the potential toxic effects of increased secretion of glucocorticoids during critical periods of brain development.