Effects Of Ketamine-induced Symptoms Similar To Schizophrenia In Mice And Its Mechanisms

Objective: To observe the symptoms similar to schizophrenia of Ketamine- induced in mice, and investigate its Mechanisms.Methods: Mice were randomly divided into 4 groups: control group,low dose Ketamine group,middle dose Ketamine group and high dose Ketamine group. Control group was intraperitoneally administered with 25 mg/kg (qd) normal saline for 7 days. Ketamine groups were respectively administered with low dose (25 mg/kg),middle dose (50 mg/kg),high dose (100 mg/kg) (qd) Ketamine for 7 days. The behavior changes of mice were observed; The levels of SOD and MDA were detected by colorimetric method; The pathological changes of hippocampus were observed by HE stain; The expressions of NRG1 and ErbB4 gene in hippocampus were detected by reverse transcription polymerase chain reaction (RT-PCR); The expressions of NOX4 and ErbB4 were detected by immunohistochemical method.Results:(1)Single or continuous administration of Ketamine could induce hyperactivity,stereotyped behabior,limp behavior and ataxia in mice (P <0.05).(2)High-dose Ketamine group could obviously reduce the activity of SOD (P <0.01), there was no difference in the level of MDA among groups (P >0.05).(3)High-dose Ketamine group could obviously decrease the expression of NRG1 and ErbB4 mRNA (P <0.05).(5)Different doses of Ketamine could increase the expression of NOX4 (P <0.01) and decrease the expression of ErbB4 (P <0.01).Conclusions: Ketamine could induce the symptoms similar to schizophrenia in mice, and its mechanisms might be involved in oxidative stress and the decrease of NRG1 and ErbB4 after administration of Ketamine.