Objective To establish a multi-drug resistant model of temporal lobe epilepsy and observe the effect of hippocampal stimulation on pharmacoresistant epileptic rats and its possible mechanism with the use of indexes including after discharges (AD) of the amygdalae,the stimulus-induced seizures and the extracellular levels of γ-aminobutyrate (GABA).Methods Totally,120 Wistar rats were used for the amygdaloid kindled model of epilepsy by chronic stimulation of amygaloid basal lateral nucleus.Based on the successful kindled model of epilepsy,we selected the pharmacoresistant and pharmacosensitive epileptic rats according to their response to phenobabital and phenytoin.We then divided the pharmacoresistant epileptic rats into the hippocampal stimulation group and control group,with 8 rats in each group.Low-frequency stimulus was conducted for two weeks in the hippocampal stimulation group.The hippocampus extracellular fluid collected by microdialysis was then used to determine the levels of GABA by a high performance liquid chromatography method after hippocampal stimulation.Results The stimulus-induced seizures were inhibited significantly,and the frequency of the AD was decreased,as well as the amplitude,compared with the control group.The extracellular level of GABA in the 8:00-9:00 am and the 8:00-9:00 pm was (32.69 ± 7.80) and (35.76 ± 6.27) μg/ml,respectively,both significantly increased as compared with the control ((26.58 ± 6.87) μg/ml,t =-21.45,P =0.000 ; (31.50 ± 4.87) μg/ml,t =-15.74,P =0.000).Conclusions The low-frequency hippocampal stimulation inhibits the seizures of the kindled model of epilepsy and decreases the frequency,the amplitude,as well as the duration of the amygdale AD in the pharmacoresistant epileptic rats,which may be contributed to the increased GABA content in extracellular fluid of the brain after stimulation.