Persistent, but Paradoxical, Effects on HPA Regulation of Infants Maternally Deprived at Different Ages.

Twenty-four hours of maternal deprivation have been shown to have immediate and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. In the first experiment the influence of such a maternal deprivation period (pnd 11-12) on basal and stress-induced ACTH and CORT levels 4 and 8 days following reunion was investigated. The results revealed a suppression of the ACTH response in the previously deprived animals which was not reflected in the CORT response. In the second experiment these persistent effects were studied in animals deprived during different stages of development. Deprivation early in development (pnd 3-4) produced an animal with a hyperreactive ACTH response whereas deprivation later (pnd 7-8, pnd 11-12) resulted in a hyporeactive ACTH response to stress at pnd 20. To study further the possible mechanisms leading to these different ACTH responses, we used in situ hybridization to investigate hippocampal mineralocorticoid (MR) and glucocorticoid receptor (GR) gene expression and corticotropin-releasing hormone (CRH) and GR mRNA levels in the paraventricular nucleus of the hypothalamus (PVN) of these 20-day old animals. Permanent changes in hippocampal GR mRNA were seen only in the later deprived pups, whereas GR mRNA was reduced in the PVN in all deprived pups. In conclusion, maternal deprivation during the neonatal period produces alterations in the ACTH response to a mild stress and sustained changes in GR transcript levels. The direction and magnitude of these effects are dependent upon the age at which maternal deprivation is experienced.