Modulatory role of ginsenosides injected intrathecally or intracerebroventricularly in the production of antinociception induced by kappa-opioid receptor agonist administered intracerebroventricularly in the mouse

We examined the effects of ginseng total saponin and several ginsenosides i njected intrathecally (Lt) or intracerebroventricularly (i.c.v.) on the ant inociception induced by U50, 488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrr olidinyl)cyclohexyl]benzeocetamide; a kappa opioid receptor agonist) admini stered i.cv. The tail-flick test was used as an analgesic assay. Total sapo nin fraction at doses of 0.1 to 20 mu g, which when administered intratheca lly (i.t.) or intracerebroventricularly (i.c.v.) alone did not affect the l atencies of tail-flick threshold, attenuated dose-dependently the inhibitio n of the tail-flick response induced by U50, 488H (60 mu g) administered i. cv. The duration of antagonistic action of total saponin fraction against U 50, 488H-induced antinociception lasted at least for 6 h. Various doses (fr om 0.1 to 1 mu g) of ginsenosides R-b1, R-b2, R-c, R-d, and Rg(1), but not R-e, injected i.t. dose-dependently attenuated antinociception induced by U 50, 488H administered i.cv. Furthermore, various doses (from 1 to 10 mu g) of ginsenosides R-b2 and R-e, but not R-b1, R-c, R-d, and R-g1, injected i. c.v. dose-dependently attenuated antinociception induced by U50, 488H admin istered i.c.v. In summary, ginsenosides R-b1, R-b2, R-c, R-d and R-g1 admin istered spinally appear to be responsible for blocking the antinociception induced by U50, 488H administered supraspinally, whereas ginsenosides R-b2 and R-e administered supraspinally appear to be responsible for blocking th e antinociception induced by U50, 488H administered supraspinally.