Regulation of forebrain glucocorticoid receptor systems and the development of individual differences in stress responses in the rat

Abstract

The development of forebrain glucocorticoid receptors exhibits a postnatal period of plasticity. Postnatal maternal deprivation, endotoxin exposure, and brief periods of postnatal handling permanently influence the levels of glucocorticoid receptors in specific brain areas known to mediate glucocorticoid negative feedback regulation of hypothalamic-pituitary-adrenal activity. The differences in receptor expression thus mediate permanent changes in stress responsivity, the direction of which is dependent on the nature of the change in glucocorticoid receptor expression. The changes in glucocorticoid receptor expression are, in turn, dependent on the specific dynamics of mother-pup interactions. In the case of postnatal handling, mechanisms relating early environment to changes in hippocampal glucocorticoid receptor expression have been identified and include a progressive signaling between the peripheral nervous system, via thyroid hormones, and the central nervous system, via serotonergic activation. Intracellular pathways have also been mapped and involve cyclic AMP activation of protein kinase A and subsequent increases in transcription factors, providing a plausible link to genomic function.