A single postnatal dose of dexamethasone enhances memory of rat pups later in life

Postnatal dexamethasone (Dex) therapy is associated with adverse neurodevelopmental outcomes, which might be related to its timing of administration. We used time-dated pregnant Wistar albino rats, whose litters were divided into experimental (Dex) and control groups intraperitoneally administered one dose of Dex (0.5 mg/kg) or normal saline (NS), respectively, at either day 1 (P1) or 7 (P7). The magnitude of the contextual freezing response and performance on the Morris water maze were significantly higher in the Dex-P7 group than in those of the other groups at P56. Dendritic spine density, membranous expression of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2A/2B, and postsynaptic density-95 (PSD-95) were significantly higher in the Dex-P7 group than in the other groups. Furthermore, cytosolic expression of nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase (PI3K) was significantly higher in the Dex group than in NS group. Moreover, Dex administration at P7 increased cell proliferation, neuronal differentiation, and the survival of newly born neurons in the dentate gyrus. These results suggest Dex at P7 enhances the acquisition of contextual fear and spatial memory later in life due to the modulation of the newly born neurons, increase in dendritic spine number, and NMDAR expression.