The mechanism of antipsychotics interfering with schizophrenic-like phenotype in early social isolation mice / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate and compare the effects and mechanisms of risperidone and haloperidol on early socially isolated mice. 【Methods】 C57BL/6 mice aged 3 weeks were raised in single cages after weaning for social isolation （SI）， and the control （GH） group was raised normally. Eight weeks later （mouse adult）， the mice received intraperitoneal injection of equal volumes of normal saline （NS）， risperidone （RIS） and haloperidol （HA）. Then they were divided into four groups： GH+NS， SI+NS， SI+RIS， and SI+HA. The dose of risperidone and haloperidol was 0.1 mg/kg and 0.2 mg/kg， respectively. After administration for 14 days， through the open field experiment， elevated plus maze experiment， forced swimming experiment， nesting experiment， social interaction experiment， novel object discrimination experiment， and prepulse suppression experiment， the mice’s schizophrenia-like behavior was evaluated in terms of autonomous activities， emotions， cognition， and social behavior. We also detected dopamine type 2 receptor （D2R） and the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex （PFC） and nucleus accumbens （NAc）. 【Results】 Compared with those in GH group， the anxiety-like behavior and depression-like behavior of SI mice were significantly increased （P<0.05）， while the nesting ability was significantly decreased （P<0.05） and social interaction and avoidance behavior were significantly reduced （P<0.05）； the cognitive function of PPI was impaired （P<0.05）. Compared with haloperidol， risperidone improved not only depression-like behavior and PPI impairment， but also anxiety-like behavior， nesting ability， social interaction， and avoidance behavior. In SI+RIS and SI+HAL groups， the content of D2R in NAC decreased significantly， and the difference of NR1 in PFC disappeared compared with the control group. 【Conclusion】 Early SI is a good model for simulating schizophrenia. Risperidone has a better intervention effect than haloperidol； risperidone and haloperidol may exert their effects through D2R and NR1.