Regulation of glucocorticoid and mineralocorticoid receptor mRNAs in the hippocampus of the maternally deprived infant rat.

The hypothalamic-pituitary-adrenal (HPA) axis in the developing rat has a limited response to acute challenges between days 3 and 14 of life. Several hypotheses have been proposed to explain this quiescent state. Immaturity of brain, pituitary and adrenal elements or excessive feedback inhibition are common explanations. Recently, a series of studies by Levine and co-workers has shown that prolonged maternal deprivation (24 h) results in increased basal and stress induced corticosterone (CS) levels. An increased adrenal response to ACTH along with an enhanced and sustained ACTH response have been implicated in this phenomenon. A brain structure that appears to be important for normal HPA function is the hippocampus, a structure rich in corticosteroid receptors, which has been hypothesized to play a role in the basal tone of the HPA and in the magnitude and duration of stress responses. Thus, to study further the possible mechanisms leading to an enhanced and sustained ACTH response that is seen in maternally deprived pups, we used in situ hybridization to investigate hippocampal mineralocorticoid (MR) and glucocorticoid receptor (GR) gene expression in 12 groups of animals: six groups involved 24 h maternally deprived (DEP) and non-deprived (NDEP) rat pups at three ages (6-, 9-, and 12-days-old); the other six groups included pups similarly treated, but challenged with an exposure to a mild stressor (saline injection) and sacrificed 1 h thereafter. We found: (1) an age effect for almost every hippocampal subfield for both MR and GR mRNAs: MR increases with age, while GR decreases: (2) down-regulation of MR mRNA in CA1 region in the DEP animals; and (3) down-regulation of GR mRNA, also in CA1, in the saline-injected DEP and NDEP animals. Our results indicate that corticoid receptors in the developing CA1 hippocampal region appear to be sensitive to circulating CS. They also suggest that the relative ratio of GR and MR in the CA1 region may contribute to the enhanced and sustained CS response seen after a mild stressor in deprived animals.