中文摘要：

目的观察甲基苯丙胺（METH）急性处理时致神经损伤情况,以及纹状体中氨基酸类神经递质谷氨酸（glutamate,Glu）、单胺类神经递质多巴胺（dopamine,DA）及其代谢产物DOPAC的变化。方法建立METH急性毒性模型,同时利用药物头孢曲松进行干预,利用清醒动物脑微透析技术检测神经递质含量的变化。结果 METH急性给药组与盐水对照组相比,刻板行为明显增加（P〈0.01）;急性给予METH后,胞外Glu浓度持续增加,在本试验检测时间（0～6 h）范围内,与基础平衡值相比,在给药5.5 h时Glu浓度已增加450%。胞外DA水平在1 h达峰值,与基础平衡值相比,浓度增加1248.6%。与METH组相比,头孢曲松预防给药可明显降低大鼠纹状体胞外Glu浓度（P〈0.05）。结论 METH急性处理能引起纹状体中胞外谷氨酸的含量明显增加,导致神经损伤;METH的神经毒性与兴奋性氨基酸的过度释放密切相关。

英文摘要：

Aim To observe the neuro-injury induced by methamphetamine（METH）acute treatment and to investigate changes of glutamate and dopamine on METH-induced nerve injury in striatum.Methods Rats were administered（ip）with METH to establish acute toxicity model,and the glutamate transporter agonist ceftriaxolne（Cef）was applied to regulate the expression of glutamate transporters.The neurotoxicity of METH was evaluated by stereotyped behavior.And the concentration of Glu,Gly,and DA in striatum were detected by microdialysis combined with HPLC-FD method.Results Brain microdialysis and high performance liquid results showed that,after acute administration of METH,extracellular Glu concentration was increased continuously during the whole detection time（0～6 h）,compared with the basal level,extracellular glutamate concentrations increased 450% at 5.5 h after METH administration.And DA concentration reached peak level at 1 h,compared with the basal level,extracellular DA concentrations increased 1248.6% at 1 h.Compared to METH group,pretreated with ceftrixone significantly decreased the extracellular Glu concentration in striatum（P0.05）.The DA concentration at 1 h was partly inhibited,but it still increased 838.4% compared with the basal level.Conclusions Neurotoxicity of METH was closely related to excessive release of excitatory amino acids.Glutamate transporter may be a drug target for controlling METH-induced neurotoxicity.