Evidence that ginsenosides prevent the development of opioid tolerance at the central nervous system

The analgesic effect of ginsenosides or morphine was first determined following intrathecal (i.t.) administration in rat tail-flick test. The effect of chronic i.t. co-administration of ginsenosides with morphine on the development of opioid tolerance were also examined using rat tail-flick test. Administration of ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner. Administration of morphine (i.t.) also produced antinociception in a dose-dependent manner. The ED(50) was 1.20 mu g (1.14-1.29 mu g). However, acute i.t. co-administration of ginsenosides with morphine was not additive in antinociception. Repeated i.t. co-administration of 200 mu g ginsenosides with 10 mu g morphine inhibited the development of tolerance induced by 10 mu g morphine in rat tail-flick test, although i.t. co-administration of 50 or 100 mu g ginsenosides with morphine was without effect. In conclusion, these results indicate that i.t. administered ginsenosides produce an antinociception in rat tail-Rick test and also prevent opioid tolerance caused by chronic treatment with morphine at the spinal sites. (C) 2000 Elsevier Science Inc. All rights reserved.