A Study Of Schizophrenia Model By Chronic And Acute NMDAR Antagonist MK-801 Exposure In Perinatal And Adult Rats

Objective1. The aim of this study was to investigate the effects of perinatal NMDAR antagonist MK-801 treatment on the behavioral and cognitive abnormalities related to schizophrenia in adulthood.2. The effects of adulthood MK-801 acute treatment on sensory gating deficits. Method1. Forty postnatal day 7 male SD rats were randomly divided into 2 groups (MK, NS, n=20). MK group was subcutaneously injected with MK-801 (0.5mg/kg) at the postnatal day 7-21, once a day; the control group was injected with saline. On day 22, each group was subdivided into two groups:group housing (GH, n=10) and social isolation housing (SI, n=10). Behavioral tests including open field test, novel object recognition test and pre-pulse inhibition (PPI) test were measured at 8-weeks-old.2. Thirty-six male SD rats were randomly divided into 4 groups (MK0.1, MK0.3, MK0.5 and NS, n=9, body weight 300-320g), The rats in experimental groups(MK0.1, MK0.3, MK0.5) were intraperitoneal injected with MK-801 at dose of 0.1mg/kg,0.3mg/kg,0.5mg/kg 20 min before PPI test respectively, the NS group received saline. Result1. In open field test, the total distance was significantly decreased in the MK group compared with control group (P<0.05)2. In novel object recognition test, the exploration time was increased for the novel object. The Recognize Index was significantly reduced in the MK group compared with control group (P<0.05)3. In the chronic MK-801 experiment,the PPI was no significant difference between the MK and NS group (P>0.05)4. In the acute MK-801 experiment, the PPI of MK0.3 and MK0.5 group was significantly reduced compared with the NS group at 75dB and 80dB pre-pulse level; While at 85dB pre-pulse level, only the MK0.5 group showed disrupted PPI compared with NS group (P<0.05) Conclusions1.The results of this study showed that perinatal MK-801 chronic treatment in SD rats is a valid developmental model for schizophrenia which showed locomoter activity and memory deficits partly simulating the negative and cognitive symptoms in schizophrenia.2. Acute MK-801 treatments in adult rats disrupt PPI in a dose-dependent manner, which simulate the sensory gating deficits in schizophrenia.