| Objectives Establish the development model of schizophrenia (SZ) by intraperitoneal injection MK-801in perinatal, and explore the performance validity of model mice and the pathological mechanisms of SZ. Explore the therapeutic effect of different doses of atypical antipsychotic risperidone (RIS) on behavioral changes in model mice.Methods Mice were divided into two groups according to sex. Male mice were randomly divided into A, B, C, D, E five groups, and female mice were randomly divided into a, b, c, d, e five groups. Pups began receiving normal saline (A and a group) or0.6mg/kg Dizocilpine (MK-801) solution (B, C, D, E group and b, c, d, e group) by intraperitoneal injection at seven day after birth (P7), once a day for5days. At P45days each group of mice received normal saline (A, B group and a, b group) or0.1mg/kg RIS solution (group C and group c) or0.3mg/kg RIS solution (group D and group d) or1mg/kg RIS solution (group E and the group e) by intraperitoneal injection, once a day for15days. The mice began to conduct behavior test from P60days.Results The locomotor activity total distance of SZ developmental model mice was significantly longer than the normal control group (p<0.05), Pre-pulse inhibition(PPI) decreased significantly (p<0.05), social interaction time significantly reduced (p<0.05), escape latency significant increased(p<0.05), Time spend in object quadrant significantly reduced(p<0.05). Different doses RIS can reverse the MK-801-induced behavioral changes in varying degrees.Conclusion Perinatal mice injected with MK-801can cause spontaneous activity increase, social interaction dysfunction, PPI damage and spatial learning and memory damage in adult, and can simulate SZ positive symptoms, negative symptoms and cognitive dysfunction. RIS can reverse MK-801-induced locomotor activity increase, social interaction dysfunction, PPI damage and the abilities of spatial learning and memory damage in mice in different degree. |
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