MK-801诱导的精神分裂症发育模型大鼠脑组织DA,DOPAC,Glu和GABA浓度的变化

摘要

Objective To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA),dihydroxy-phenyl acetic acid (DOPAC),glutamate (Glu),and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats.Methods A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6:an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10,0.1 mg/kg,Bid),a chronic medication model group (intraperitoneal injection at the postnatal day 47-60,0.2 mg/kg,Qd),and a normal control group (injection with O.9% normal saline during the corresponding periods).DA,DOPAC,Glu,and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique.The utilization rate of DA and Glu was calculated.Results Compared with the normal control group,the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased ( P ＜ 0.05 ),and the GABA concentration and Glu utilization rate in the mPFC also decreased (P ＜ 0.05 ).Compared with the chronic medication model group,the DA concentration of the mPFC in the SZ developmental group decreased ( P ＜ 0.05 ),and the DOPAC concentration and the utility rate of DA in the hippocampus also decreased (P ＜0.01,P ＜0.05,respectively).Conclusion The activities of DA,Glu and GABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.%目的:通过对MK-801诱导的精神分裂症（schizophrenia,SZ）发育模型大鼠和慢性给药模型大鼠脑组织多巴胺（dopamine,DA）、二羟苯乙酸（dihydroxy-phenyl acetic acid,DOPAC）、谷氨酸盐(glutamate,Glu)和γ-氨基丁酸（γ-aminobutyric acid,GABA）浓度的比较研究,探讨围产期N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体阻断致SZ的神经生化机制.方法:60只新生雄性SD大鼠于出生后6天按批次随机分为SZ发育模型组(MK-801F)、SZ慢性给药模型组(MK-801M)和正常对照组（Control）；SZ发育模型大鼠于出生后7 ～10d皮下注射MK-801(0.1 mg/kg,Bid),SZ慢性给药模型大鼠于出生后47 ～60 d腹腔注射MK-801(0.2 mg/kg,Qd),对照组大鼠于相应时段注射0.9％的生理盐水.出生后第60天分批进行行为学测试,出生后第63天取各组大鼠大脑内侧前额叶皮质（medial prefrontal cortex,mPFC）和海马组织并匀浆,以高效液相色谱-库仑阵列电化学法检测组织匀浆中的DA,DOPAC,Glu和GABA水平,并计算分析DA和Glu的利用率.结果:SZ发育模型大鼠mPFC和海马DA及DOPAC的浓度较正常对照组明显降低(P ＜0.05)；mPFC区GABA浓度和Glu利用率较正常对照组明显降低(P＜0.05)；mPFC区DA浓度较SZ慢性给药模型组明显降低(P＜0.05)；海马DOPAC浓度及DA利用率较SZ慢性给药模型组明显降低（分别P＜0.01,P＜0.05）.结论:SZ发育模型成年大鼠mPFC区DA,Glu和GABA系统功能减退,海马DA系统功能减退.