Antagonism of U-50,488H-induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms.

Morphine-induced antinociception was prevented by pretreatment with ginseng total saponins in the tail-pinch and tail-flick tests carried out in mice. The antinociceptive effect of U-50,488H, a selective kappa-opioid receptor agonist, was prevented by naloxone, a nonselective opioid receptor antagonist, in the tail-pinch but not in the tail-flick test. However, U-50,488H-induced antinociception was prevented by ginseng total saponins in the tail-flick but not in the tail-pinch test. These results indicate that nonopioid mechanisms are involved in the antagonism of U-50,488H-induced antinociception by ginseng total saponins. In addition, the antagonism of U-50,488H-induced antinociception in mice pretreated with ginseng total saponins was abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan, but not by a noradrenaline precursor, L-dihydroxyphenylalanine, in the tail-flick test. Therefore, it appears that the antagonism of U-50,488H-induced antinociception by ginseng total saponins is dependent on serotonergic mechanisms.