Studies On The Relationship Between Glutamatergic Mechanism And Oxidative Stress Of Schizophrenic Model Induced By NMDA Receptor Antagonists

At present, schizophrenia remains the most morbid and debilitating of all psychiatric disorders and the fundamental pathological processes associated with schizophrenia remain uncertain. Undoubtedly, the development of more effective treatments depends on a better understanding of the underlying functional pathology of schizophrenia and the development of appropriate animal models, so that novel mechanistic ideas and pharmacotherapeutic approaches can be tested. Based on the glutamate (Glu) dysfunction hypothesis for the pathophysiology of schizophrenia, the relationship between glutamatergic mechanisms and oxidative stress induced by NMDA receptor antagonists were investigated by using behavioral, immunohistochemistry and neurobiochemical methods.Firstly, MK-801 and ketamine (KET), noncompetitive NMDA receptor antagonists, were administered to mice by different dosages to investigate the change of behaviors in locomotion test, stereotyped test, pole test and traction test. The results indicated that MK-801 (0.3 mg/kg, 0.6 mg/kg and 1.5 mg/kg) and KET (25 mg/kg, 50 mg/kg and 100 mg/kg) acute administration could induce schizophrenic symptoms of mice and the middle and high dosage groups were more significant than the low dosage group. After repeated administration, the behaviors of MK-801 and KET groups were significantly decreased compared with the control group in the pole test and traction test. The locomotion numbers of low dosage groups increased concomitantly with the time of administration. However, the middle and high dosage groups were opposite. The scores of stereotyped behavior gradually increased concomitantly with the time of administration. The differences between acute and repeated administration suggested there existed different mechanisms induced their behaviors.The results hereinbefore indicated that MK-801 at 0.6mg/kg could induce hyperlocomotor, stereotypy and ataxia, and was suitable for the further mechanical experiment. As a result, we investigated the effects of single and repeated administration of MK-801 (0.6 mg/kg) on extracellular Glu, ascorbic acid (AA), Dopamine(DA), 3,4-Dihydroxyphenylacetic acid (DOPAC) and Homovanillic acid (HVA) release in the...