Objective To explore the effects of astrocytes on the N-ethylmaleimide-sensitive fusion protin,(NSF) and AMPA receptor of the neurons as well as their function in epileptogenesis. Methods ACM was injected into lateral ventricle of SD rats and the behaviour changes were observed; Immunohistochemical method was used to assess the changes of the expression of NSF in the cerebral cortex and hippocampus; The cultured neurons were divided into control group, ACM group and CNQX+ACM group at random, immunocytochemistry was used to assess the changes of the expression of NSF, Western blotting was used to assess the changes of the content of NSF of the cultured neurons. Results Seizure was observed in ACM group 30 min after injecting ACM. the immunoreaction of NSF in hippocampus and cerebral cortex of rats were depressed than those of the control group 2h, 4h after injecting ACM (P<0.05); The immunoreaction of NSF in cultured neurons of the ACM group was weaker than those of the control group 4h, 8h after ACM (P<0.05). By mean of Western blotting, the concentrations of NSF of cultured neurons were depressed than those of the control group and the CNQX+ACM group 4h, 8h after ACM (P<0.05). Conclusion The results mentioned above indicated that the ACM can be reduced the expressions of NSF and result in epileptogenesis. CNQX can anatagonize this effect, showing that the downregulation of ACM on NSF of rats and cultured neurons was partly mediated by AMPA receptor.