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

The analgesic effect of ginsenosides or morphine was first determined follo wing intrathecal (i.t.) administration in rat tail-flick test. The effect o f chronic i.t. co-administration of ginsenosides with morphine on the devel opment of opioid tolerance were also examined using rat tail-flick test. Ad ministration of ginsenosides (i.t.) produced a weak antinociception in a do se-dependent manner. Administration of morphine (i.t.) also produced antino ciception in a dose-dependent manner. The ED50 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 toleranc e induced by 10 mu g morphine in rat tail-flick test, although i.t. co-admi nistration 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 to lerance caused by chronic treatment with morphine at the spinal sites. (C) 2000 Elsevier Science Inc. All rights reserved.