A Study Of Schizophrenia Model With Selective Memory Defect Induced By MK-801

Objective:NMDA receptor antagonist MK-801was injected into adult SD rats, as an animal model of schizophrenia. We intended to investigate the behavior change of the rats induced by different doses of MK-801through three tests, spontaneous locomotion, pre-pulse inhibition, and novel object recognition and found a reliable cognitive deficit model and a suitable dose of the drug for application in future study of schizophrenia model.Method:195rats were divided into experiment groups and control group. The experiment groups were treated by MK-801at the doses of0.01mg/kg,0.03mg/kg,0.1mg/kg and0.3mg/kg, with an intraperitoneal injection. Another control group was received with saline. Then, open field test pre-pulse test novel object recognition test were conducted respectively.Result:1. Effects of different doses of MK-801on locomotionThe rats showed increased spontaneous activity and mild ataxia in the experiment groups. The spontaneous activities was significant increased after the treatment of MK-801, and induced dose-dependent behavioral manifestations. The0.3mg/kg group in the50min-90min exhibited a significant difference (P<0.05) compared with control group.2. Effects of different doses of MK-801on sensorimotor gating(1).MK-801decreased remarkably PPI percentange at all three pre-pulse levels at a dose threshold of0.1mg/kg. PPI was damaged at the dose range of MK-801, and different pre-stimulus intensities also had an impact on PPI (P<0,001).(2).There was significant difference on shock reflection amplitude between the different treated groups and control group (P<0.05). Further analysis, we found the amplitude of shock reflection at medium doses of the drug is significant greater than control group.3. Effects of different doses of MK-801on NORTMK-801decreased the NOR index significantly (P<0.05). Post-Hoc comparisons showed that the effect mainly originated from differences between the NS group and the MK-8010.03mg/kg group (P<0.01).0.1mg/kg group also showed a much lower NOR index than control group (P<0.05).Conclusion:1. Spontaneous activities show a dose-dependent behavioral effect. The performance of rats at0.3mg/kg dose simulates schizophrenia positive symptoms.2. Adult SD rats with injection of MK-801can cause different degree of damage in PPI.The0.1mg/kg of MK-801is an appropriate dose to induce schizophrenia animal model of sensorimotor gating defect.3. Adult SD rats with acute injection of MK-801cause visual and episode memory damage, and0.03mg/kg is a relatively ideal, pure, and appropriate dosage. NORT is a useful tool in preclinical research on putative memory enhancers in schizophrenia and in studies of the specific neural mechanisms underlying memory impairments in schizophrenia.