Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway

Adrenal steroids and N-methyl-D-aspartate receptor activation have both been shown to regulate the rate of proliferation of granule neuron progenitor cells in the dentate gyrus of adult rats (Cameron H. A. and Gould E. (1994) Neuroscience 61, 203-209; Cameron H. A. et al. (1995) J. Neurosci. 15, 4687- 4692]. Parallels between the actions of these two factors suggest that they may regulate cell division through a common pathway. This hypothesis was tested by altering both of the factors simultaneously and determining whether the effects were additive. The results of this study demonstrate that alterations in N-methyl-D-aspartate receptor activation block the effects of corticosterone level on cell proliferation; N-methyl-D-aspartate blocks the adrenalectomy-induced increase in [³H]thymidine-labelled cell density in the dentate gyrus, whereas the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (MK-801) prevents the corticosterone-induced decrease in proliferating cells. This finding suggests that adrenal steroids and N- methyl-D-aspartate receptor activation regulate granule cell production in the adult rat dentate gyrus through a common pathway and that N-methyl-D- aspartate receptor activation operates downstream of corticosterone in this pathway.