OBJECT: In order to examine the interaction mechanisms of electroconvulsive shock(ECS) and antipsychotic drug at the level of molecular biology, we observed the effect of chlorpromazine pre-treatment on the activation of mitogen activated protein kinase(MAPBD induced by electroconvulsive shock(ECS) in rat hippocampus. METHODS: Male Sprague-Dawley rats were divided into 2 groups. To the experimental group chlorpromazine(20mg/kg) was given intraperitoneally, 3nd to the control disliked water was given instead. Thirty minutes later, ECS was given and the hippocampus was dissected out 2 minutes thereafter. Immunoblotting with antiphosphotyrosine antibody was carried out, and the signal intensity at 42kDa band was quantitized using densitometer. The obtained result was compared by student t-test between the experimental and the control group. The absolute amount of MAPK was measured by immunoblotting with anti-MAPK antibody. RESULT: The tyrosine phosphorylation of MAPK reached peak at 2 minutes after ECS. However, in the chlorpromazine pre-treated group, the peak level of MAPK tyrosine phosphorylation was significantly attenuated(t= -3.12, df= 14, p=0.008) compared to the control. In contrast to this, the absolute amount of MAPK did not differ between the pretreated and the control group. CONCLUSION: Chlorpromazine attenuated the tyrosine phosphorylation of MAPK by ECS. This finding seems to be related to the fact that chlorpromazine pre-treatment changed the c-fos expression by ECS in rat brain. Antipsychotic drug and ECS might interact at the level of MAPK signal transduction system, and this might explained the observed synergistic elect of two treatment modality.