| OBJECT: 1. To make a corresponding improvement of the hardware facilities & optimize the analytical software of the Morris Water Maze online detection & analysis system based on the preliminary R & D works of our laboratory .And to aim directly at the newly raised ethology evaluation index to take an verification test.2. It is clear that Ginsenoside and its main components Rg1, Rb1 have the effects of promoting the dysfunction of learning and memory. But the comparative efficacy research of total ginsenoside, monomer Rg1, Rb1 and monomer composition Rg1+Rb1 in improving cognitive impairment of ethanol-induced animal model was not been reported. The aim of this research work was to find whether monomer composition Rg1+Rb1 was a theoretically new type compound medicine which had equivalence or better potency than GTS or saponin monomer .METHOD: 1. To improve the Morris Water Maze online detection & analysis system based on preliminary studies on the behavior testing equipment of our laboratory. To improve the hardware and optimize the software of the equipment. And to aim directly at the newly raised ethology evaluation index and new testing method to operate verification test to make sure the reliability of the instruments and the sensitivity of the ethology evaluation index.2. To prepare acute and chronic ethanol-induced cognitive dysfunction animal model with acute injection and chronic intragastric administration of ethanol. Using intragastric administration of GTS (25mg/kg,50mg/kg, 100mg/kg),Rg1 (3mg/kg, 6mg/kg,12mg/kg),Rb1 (3mg/kg,6mg/kg,12mg/kg) and compound Rg1+Rb1 (1.5+1.5mg/kg, 3+3mg/kg, 6+6mg/kg) to improve this impairment. Using improved Morris Water Maze online detection & analysis system for spatial learning and memory behavior tests. And to find pathological changes in hippocampus of mice brain tissue with HE staining.To find the expression changes of GABAB & NMDAR1 receptor in hippocampus CA1 area with immunohistochemistry.RESULT: 1. The improved Morris Water Maze online detection & analysis system performance was reliable. Verification test for ethology evaluation index & testing method of different animal models was creditable.2. GTS high dose (100mg/kg), low doses of Rg1 monomer (3mg/kg) and monomer composition low-dose (1.5+1.5mg/kg) could improve the acute alcohol-induced spatial cognitive impairment in water maze test. GTS mid-dose (50mg/kg), high-dose (100mg/kg) and monomer composition of low-dose (1.5+1.5mg/kg) could promote working memory in water maze test. GTS mid-dose (50mg/kg), Rg1 mid-dose (6mg/kg), monomer combination low-dose (1.5+1.5mg/kg), high-dose (6+6mg/kg) could improve chronic ethanol-induced cognitive dysfunction in water maze test, while the improvement effects of saponin in step-down passive avoidence test was not significant. HE staining showed that acute and chronic ethanol administration could make place-cells in hippocampal CA1 area loose and atrophic, and saponin groups had different protective effects levels. Immunohistochemistry results showed that acute ethanol intake could increase the GABAB receptor expression in hippocampal CA1 area and reduced the expression of NMDAR1 receptor. Chronic ethanol intake could increase the over expression of NMDAR1 while the saponin groups can reduce the over expression .
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