We have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of G protein expression in the central nervous system in rat brain. The effects of continuous infusion of ginsenosides on the modulation of G protein alpha-subunit mRNA were investigated by using in situ hybridization study. Rats were infused with ginsenoside Rc or Rg1 (10 microg/10 microl/h, i.c.v.) for 7 days, through preimplanted cannula by osmotic minipumps. The level of Gas mRNA was not changed by the infusion of ginsenoside Rc or Rg1. The level of Galphai mRNA was significantly elevated in frontal cortex and hippocampus following treatment with ginsenoside Rc as well as ginsenoside Rg1. However, the level of Galphao mRNA was significantly decreased in part of the hippocampus and cerebellum after the animals had received ginsenoside Rg1 infusion. These results suggest that prolonged infusion of ginsenosides could differentially modulate the expression of G protein alpha-subunit mRNA in rat brain in a region-specific manner.