ABSTRACT
Based on the glutamate dysfunction hypothesis for the pathophysiology of schizophrenia, MK801, a noncompetitive antagonist for the NMDA-type of glutamate receptors, was administered to mice by i.p. injection. We observed hyperlocomotion and stereotypy, two behavioral signs indicative of schizophrenic symptoms in human. Aided with automated movement measuring of locomotion and videotaping for off-line scoring of stereotypy, these two schizophrenia-like behaviors were readily evaluated. According to the result of dose-response measurements of serial MK801 dosages in the BALB/c inbred mice, 0.6 mg/kg MK801 was determined as the optimum dosage for these behaviors. Furthermore, the same experiments were performed in another inbred strain C57BL/6 and the outbred stock ICR, and similar results were obtained. These results show that MK801 induces schizophrenia-like symptoms in both inbred and outbred mice. Risperidone, an atypical antipsychotic drug for treating schizophrenia in human, was used in the schizophrenia models using BALB/c and C57BL/6 mice. The results indicated that risperidone dose-dependently inhibited the MK801-induced schizophrenia-like symptoms in BALB/c and C57BL/6 mice. Thus, our results indicate that the MK801-induced behaviors may serve as useful mouse models of schizophrenia.