The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 microg/ml) or tap water (Veh) from gestational day 15 until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.

Corticotropin-releasing hormone (CRH) acts within the brain and pituitary to coordinate the overall endocrinological and behavioral stress response. From postnatal day (PND) 4 to 14, the infant rat displays minimal adrenal response to mild stress. However, maternal deprivation alters the pituitary-adrenal system such that the infants become responsive to specific stimuli. We hypothesized that maternal deprivation would also affect CRH brain circuits. Since tricyclic antidepressants have been shown to decrease the adrenal response to stress in adult rats, we hypothesized that CRH-related changes induced by maternal deprivation would be prevented by this treatment. Thus, we investigated CRH-related molecules on animals that were maternally deprived on PND 13 compared with nondeprived animals. We found that maternal deprivation caused alterations in the gene expression of both CRH receptors (CRHr) 1 and 2 in specific brain regions, and that some of these effects were augmented by chronic isotonic saline injections. There was a significant increase in CRH, CRHr1, and r2 mRNA in the cortex. In amygdala, CRHr1 and r2 mRNAs were decreased. CRHr2 mRNA was also decreased in the ventromedial nucleus of the hypothalamus, whereas an increase was detected in the hippocampal pyramidal cells. One week of desipramine (DES) administration preceding the maternal deprivation event prevented all the deprivation-induced changes in CRHr2 mRNA, regardless of the direction of the original change. We also found that chronic injection treatments enhanced the adrenocortical response and improved the efficiency of negative feedback in maternal deprivation animals. These results demonstrate that maternal deprivation elicits modifications of CRH brain circuits in a site-specific manner, and that the regulation of CRHr2 gene expression is mediated by mechanisms different from those involved with the modulation of CRHr1 in the infant rat.