目的:观察丙戊酸(valproate,VPA)对戊四氮(pentylenetetrazol,PTZ)点燃的自由活动大鼠海马胞外兴奋性氨基酸类神经递质动态释放过程的影响。方法:建立大鼠慢性癫癎模型及自由活动的清醒动物脑内在体微透析(microdialysis,MD)模型,用高效液相色谱测定急性腹腔注射VPA 200 mg·kg-1对大鼠海马胞外兴奋性氨基酸类神经递质释放的影响。结果:在惊厥发作期及发作间期,自由活动大鼠海马胞外谷氨酸及天冬氨酸水平显著上升,给予VPA 200 mg·kg-1后,两者浓度明显下降。结论:①VPA对海马胞外主要的兴奋性氨基酸类神经递质释放的调控为其发挥抗癎作用的重要机制之一;②在VPA对CNS兴奋性氨基酸类神经化学递质调控机制的研究中,PTZ点燃的大鼠癫癎模型较为理想。 Objective: To investigate the effect of valproate (VPA) on the dynamic release of extracellular excitatory amino acid neurotransmitters in hippocampus of rats exposed to pentylenetetrazol (PTZ). Methods: Chronic epilepsy model and free-moving conscious intracerebral microdialysis (MD) models were established in rats. Extra-cellular excitability of rat hippocampus was detected by high performance liquid chromatography (RP-HPLC) at a dose of 200 mg · kg-1 Effect of Sexual Amino Acids on Neurotransmitter Release. Results: The levels of extracellular glutamate and aspartate in hippocampus of free-moving rats increased significantly during the episodes of seizures and seizures. The concentrations of VPA and 200 mg · kg-1 VPA decreased significantly. CONCLUSION: (1) VPA can regulate the release of extracellular excitatory amino acid neurotransmitters in hippocampus as one of the important mechanisms of its anticholinergic activity. (2) In the study of the regulation mechanism of VPA on neurotransmitter of excitatory amino acids in CNS, PTZ-lit rat epilepsy model is ideal.