Glucocorticoid (GC) acts through both genomic and nongenomic mechanisms. It affects the structure and function of the central nervous system (CNS), especially the hippocampus. Here we report an in vitro culture system that can yield embryonic hippocampal neurons deficient in the expression of glucocorticoid receptor (GR) as demonstrated by immunoblotting, immunocytochemistry and RT-PCR. Owing to this unique feature, those neuron preparations can serve as an ideal model for studying the nongenomic actions of GC on neural cells. In this study, we found that the Erk1/2, JNK, and p38 mitogen-activated protein kinases (MAPKs) were activated in these neurons by BSA conjugated corticosterone (B-BSA) within 15min of treatment. This activation was not blocked by RU38486, spironolactone or cycloheximide. Therefore, it is concluded that the activation of MAPKs observed here was due to the nongenomic action of GC. Furthermore, a 24 h incubation with corticorsterone (B) at concentrations ranged from 10^-11M to 10^-5M did not have effect on the viability of GR-deficient neurons.