Glucocorticoids (GCs) have been shown to affect the development and differentiation of a number of tissues. High perinatal GCs act on the developing central nervous system to permanently alter behavior, homeostatic control mechanisms, and the morphology and physiology of the brain. However, most studies in this area have been pharmacological in nature. In the rat, elevating endogenous GC levels during the perinatal period has been difficult, as there are mechanisms during this period, whereby GC levels are maintained at low and constant levels. Between days 4 and 14, pups do not show a GC response to stressors which, in the adult, normally lead to large GC elevations. This period is known as the """"""""stress hyporesponsive period"""""""" (SHRP). However, we have recently observed that following 24 hr of maternal deprivation, rat pups show a marked increase in their GC response to stress (novelty) and ACTH administration at ages at which nondeprived pups show none. Using the maternal deprivation paradigm, we can now elevate endogenous GCs during critical periods of development, and thus, study the neuroendocrine and behavioral consequences of these elevated GCs. Stress during pregnancy in the human has been reported to have deleterious effects on the physiological and psychological development of the child. Many neural systems which develop prenatally in the human do so postnatally in the rat. Thus, the neonatal rat may constitute a good animal model in which to study the effects of GCs on these developmental processes. The proposal has four specific aims: 1) To examine which components of the hypothalamic-pituitary-adrenal system (HPA) are modified by maternal deprivation. GCs, ACTH, CRF, and glucocorticoid receptors will be studied during the 24 hr period of maternal deprivation. 2) To examine which aspect of maternal behavior is responsible for inhibiting the HPA system in the rat pup. 3) To examine whether perinatal maternal deprivation influences the subsequent activity of the HPA system and behavior during the pre- and postweaning period. 4) To examine whether perinatal maternal deprivation alters neuroendocrine activity and behavior in adulthood.
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