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We investigated the influence of centrally administered ginsenoside on the regulation of mRNA levels of the family of NMDA receptor subtypes (NR1, NR2A, NR2B, NR2C) by in situ hybridization histochemistry in the rat brain. The ginsenosides Rc and Rg1, the major components of ginseng saponin, differentially modulate NMDA receptor subunit mRNA levels in rat brain following prolonged i.c.v.-infusion. Ginsenosides Rc or Rg1 (10 microg/10 microl/hr for 7 days) was infused through preimplanted cannulae connected to osmotic mini-pumps. The level of NR1 mRNA is significantly increased in temporal cortex, caudate putamen, hippocampus, and granule layer of cerebellum in Rg1-infused rats as compared to control group. The level of NR2A mRNA is elevated in the frontal cortex. In contrast, it was decreased in CAI area of hippocampus in Rg1-infused rats. However, there was no significant change of NR1 and NR2A mRNA levels in Rc-infused rats. The level of NR2B mRNA is elevated in cortex, caudate putamen, and thalamus in both Rc- and Rg-infused rats. In contrast, NR2B level is decreased in CA3 in Rg1-infused rats. The level of NR2C mRNA is increased in the granule layer of cerebellum in only Rg1 but not Rc infused rats. These results show that structure difference of ginsenoside may diversely affect the modulation of expression of NMDA receptor subunit mRNA after infusion into cerebroventricle in rats.