Effects of ZDY101, an active component from Zhimu, on rat dementia model produced by intracranial injection of ibotenic acid

A dementia model was produced in adult Sprague-Dawley rats by bilateral injection of ibotenic acid, 2μg in 0.5 μL per side, into basal ganglion. ZDY101, 3.6, 18, 90 mg·kg-1·d-1, was given through gastric tube to 3 groups of the model rats for 90 days. The learning and memory ability of model rats without treatment declined compared with sham-operated controls, the composite index (number of wrong response in 5 min divided by latent period) being 0.71 ± 0.30 vs 0.10 ± 0.13 respectively. The brain M receptor density also decreased as compared with sham-operated controls, being 891 ± 150 vs 1039 ± 214 fmol·mg-1 protein respectively. ZDY101 simultaneously up-regulated the brain M receptor density and improved the memory and learning ability of model rats. For the middle dose group, the M receptor density was 1028 ±145 fmol·mg-1 protein (P<0.05) and the composite index of step-through test was 0.20 ± 0.18 (P<0.01). Since there was a significant correlation between M-receptor density and result of step-through test, it is apparent that the mechanism of action of ZDY101 is quite different from that of cholinesterase inhibitor. It is highly probable that the improvement of memory was due to the up-regulation of brain M receptor density. (authors)