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

Abstract

We examined the effects of ginseng total saponin and several ginsenosides injected intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on the antinociception induced by U50, 488H (trans-3,4-dichloro-N-methyl-N-[2- (1-pyrrolidinyl)cyclohexyl]benzeocetamide; a kappa opioid receptor agonist) administered i.c.v. The tail-flick test was used as an analgesic assay. Total saponin fraction at doses of 0.1 to 20 micrograms, which when administered intrathecally (i.t.) or intracerebroventricularly (i.c.v.) alone did not affect the latencies of tail-flick threshold, attenuated dose-dependently the inhibition of the tail-flick response induced by U50, 488H (60 micrograms) administered i.c.v. The duration of antagonistic action of total saponin fraction against U50, 488H-induced antinociception lasted at least for 6 h. Various doses (from 0.1 to 1 microgram) of ginsenosides Rb1, Rb2, Rc, Rd, and Rg1, but not Re, injected i.t. dose-dependently attenuated antinociception induced by U50, 488H administered i.c.v. Furthermore, various doses (from 1 to 10 micrograms) of ginsenosides Rb2 and Re, but not Rb1, Rc, Rd, and Rg1, injected i.c.v. dose-dependently attenuated antinociception induced by U50, 488H administered i.c.v. In summary, ginsenosides Rb1, Rb2, Rc, Rd, and Rg1 administered spinally appear to be responsible for blocking the antinociception induced by U50, 488H administered supraspinally, whereas ginsenosides Rb2 and Re administered supraspinally appear to be responsible for blocking the antinociception induced by U50, 488H administered supraspinally.