Effects of prenatal dexamethasone on spatial learning and response to stress is influenced by maternal factors

The present study investigated the effect of prenatal dexamethasone (Dex) e xposure on early perinatal events, hippocampal function, and response to st ress. Pregnant rats received Dex in the evening water (2.5 mug/ml) or tap w ater (Veh) from gestational day 15 until delivery. On the day of parturitio n, pups were randomized, cross-fostered, and reduced to eight or nine per d am. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, reari ng mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex . Spatial visual memory was evaluated with the Morris water maze. The corti costerone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determi ned by in situ hybridization. Exposure to Dex caused restlessness in mother s, low birth weights, and poor weight gain in the offspring. The Dex-Dex ma les had impaired spatial learning, inability to rapidly terminate the adren ocortical response to stress, and decreased hippocampal glucocorticoid rece ptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-t reated mothers had adequate spatial learning, enhanced glucocorticoid feedb ack, and increased hippocampal GR mRNA. We conclude that the environment pr ovided by a healthy mother during the postnatal period can prevent the detr imental effects of prenatal Dex administration on cognition, GR mRNA expres sion of the hippocampus, and the quality of the stress response.