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Objective: To study the role of Ginsenoside Rgl on improving cognitive impairment of neurodegenerative diseases,dual-probe brain microdialysis was used to simultaneously investigate the effects of Rgl on extracellular acetylcholine(ACh),Choline(Ch),glutamate(Glu) and taurine(Tau)in medial prefrontal cortex(mPFC)and hippocampus(Hip)of the awake rats.Method: Male SD rats were randomly divided into normal group(C),model group (M),Rg1 group (Rg1,20 mg · kg-1),and 6 rats from each group.In group Rg1,the rats received Rg1via intraperitoneal (i.p) injection 8 days,which do.On the 7th day,two probe cannulas were implantated in mPFC(A:+ 3.2 mm,R:-1.5 mm,V:-2.0 mm,inclination 10o)and Hip(A: -5.6 mm,R:+4.6 mm,V:-3.4 mm)of rats brain.The next day,the probes were inserted in two-site of brain of awake rat.Group C was perfused(1.5 μl · min-1) with modified Ringers solution (containing neostigmine 2 μmol · L-1,N-Ringer) and collected for 540 min.Group M and Rg1 were perfused with N-Ringer and balanced for 2 h,then the dialysate were collected 80 min as a basis for the level values.Then reperfusion with NaN3-N-Ringer (containing NaN3 50 μmol · L-1 and neostigmine 2 μmol · L-1) was 120 min,and then converted N-Ringer to perfuse 340 min.In group Rg1,Rg1 was administrated via i.p as soon as the perfusion with NaN3-N-Ringer was end,and then continuous collection 340 min.HPLC-IMER-ED and HPLC-Fluorescence were used to determine of acetylcholine and amino acid neurotransmitters.Results: Compared with group C,NaN3 reduces significantly extracellular Ach in mPFC (40,80 min,P <0.05) and Hip (80 min,P <0.05) at the meantime,but increases significantly Ch in mPFC (40 ~ 160、320、400 ~ 440 min,P <0.05 or P <0.01) and Hip (120 ~ 160 min,P <0.01),Glu in mPFC (40 ~ 120,280 ~ 440 min,P <0.05 or P <0.01) and Hip (80 ~ 160 min,P <0.05 or P <0.01),similarly increases Tau (80 ~ 120 min,P <0.01) in mPFC and H.Compared with group M,Rg1 could significantly increase Ach in mPFC (160 min,P <0.05) and Hip (160 ~ 240 min,P <0.05),significantly reduce Glu in mPFC (40 ~ 440 min,P <0.05,0.01 and 0.001) and Hip (160,280,320 and 360 min,P <0.05),as the same time,lower Tau in mPFC (80 ~ 120,200 and 280 min,P <0.05 or 0.01) and Hip (280 min,P <0.05).Conclusion: Rg1 can increase Ach and Ch in mPFC and Hip to enhance central cholinergic system function,while it can inhibit the neurotoxicity of excitatory amino acids (Glu and Tau),this may be one of the main factor of Rg1 in improving cognitive impairment.