Study On The Schizophreniform Symptoms Of The Mice Induced By Ketamine And Effects Of MAPK Signal Pathway

Objective: To establish mice model of schizophrenia by ketamine, and investigate the effect of MAPK signal pathway.Methods: 50 mice were randomly divided into saline control group,Ketamine groups including high,middle and low dose group,and Clozapine group.All mice except the Clozapine group's were administrated by intraperitoneal injection,and the changes of their behavior were observed after 7 days.The Clozapine group's were administrated ketamine by intraperitoneal injection for 7 days,and then intragastric administration Clozapine for 7 days, and the changes of their behavior were observed after 14 days; Creatine Kinase(CK) and Nitric Oxide (NO) in serum and brain tissue were assayed;and the impact on associated protein of MAPK signal pathway was detected by RT-PCR and immunohistochemistry.Results: (1) Observation of behavior:Schizophreniform behavioral response was induced by Ketamine, including autonomous activities increased(P<0.01),stereotyped behavior scored higher (P<0.01),forced swimming immobility time prolonged (P<0.01),the number of correctly learned Y maze reduced(P<0.01,P<0.05). The behavior changes of the group's which under the clozapine treatment had a certain improvement, and with significant statistical difference compared to the High-dose Ketamine group's(P<0.01,P<0.05).(2) Results of biochemical indicator: The activity of CK in the serum of the Ketamine groups'was increased ,especially in the High-dose group's(P<0.01);the content of NO was also increased (P<0.01). The activity of CK in the brain tissue of mice of the Ketamine groups'was increased (P<0.01, P<0.05);the content of NO was remarkably increased in the High-dose group's(P<0.01). But the Clozapine group's was not increased, and there was no significant difference between them.(3) Results of the RT-PCR showed that:the High-dose Ketamine group's had obviously downed the gene expression of ERK1/ERK2 signal pathway, and the expression of MEK1,ERK2,C-JUN genes were reduced (P<0.01,P<0.05);In the signal pathway of the ERK5,the expression of MEK5αgene was decreased (P<0.05),but the expression of MEF2C had no significant difference. (4) Immuno- histochemistry results also confirmed that: the expression of ERK2 was decreased in protein levels(P<0.05).Conclusion: The symptoms of schizophreniform could be induced by ketamine, that might be relate to the activity of CK and the content of NO in serum and tissue of brain,and the mechanism is that might be relate to inhibit the expression of the genes of the ERK1/ERK2 signal pathway.