Abstract:

Abstract:Objective
To investigate the neuroprotective effect of antipsychotic drug quetiapine and to demonstrate the mechanism of neuprotective effect. Methods Primary cultured hippocampal neurons were injured with glutamate (Glu) to set up Glu-injured model and to simulate the pathological changes in depression.Three groups were included in the experiment:control group,Glu model group and quetiapine administration group.The   survival rates in various groups were  detected by MTT method;the release level of LDH,the activity of GSH,the activity of SOD,and the level of MDA were detected before and after treated with different doses of quetiapine(50,100,200 and 500 μmol•L^-1) by enzyme detection kits.Results The survival rate of neuron in Glu model group was decreased compared with control group,almost 50% of normal data (P<0.05);but compared with Glu group,the rate was increased when the concentration of  quetiapine was 200  μmol•L^-1 (P<0.05). The LDH release level in  Glu model group was  increased dramatically compared with control group,up to  7.4 times of control group (P<0.001);compared with Glu group,the LDH release level was decreased in quetiapine group (P<0.01).The  GSH activity in Glu model group was decreased to  9.2 % of control group (P<0.05),which was increased in quetiapine group compared with Glu model group (P<0.05).The  SOD activity in Glu model group was decresded significantly compared with control group (P<0.01),which was 3.8 times of that in  Glu model group when the concentration of quetiapine was 10  μmol•L-1 (P<0.001).The MDA level in Glu model group was increased,nevertheless,which was reduced in quetiapine administration group compared with Glu model group (P<0.01).Conclusion Quetiapine possesses the neuroprotection and the mechanism may involve that it can elevate the GSH activity and SOD activity as well as decrease the level of MDA.

Key words: quetiapine;antipsychotic drugs;neuroprotective agents;glutamate;neurons