The antiepileptic effect of 4-amino-2-methyl-cantharidinimide(AMC) was reported,but its mechanism remains unknown.In this study,we investigated the effects of AMC on a rat model of penicillin-induced epilepsy.The doses of 88 and 22 mg/kg AMC and the dose of 154 mg/kg sodium valproate(VPA) were administered intragastrically(i.g.) 30 min before penicillin injection,respectively.The epileptiform activity was verified by electrocorticographic(ECoG) recordings.The levels of GABA and GABAC receptors in hippocampus were determined by immunohistochemistry,and real-time polymerase chain reaction(RT-PCR) technique was used to detect the mRNA expression of GABAC receptor ρ2.The mean frequency and amplification of spike epileptiform activity were significantly decreased in AMC and VPA-pretreated rats compared with those of non-pretreated penicillin-induced epilepsy(PIE) group.The levels of GABA,GABAC receptors and the mRNA expression of GABAC receptors ρ2 in AMC and VPA-pretreated rats were significantly increased as compared with PIE group.These findings indicate that AMC and VPA have an antiepileptic effect on PIE in rats,and the antiepileptic effect of AMC may be mediated by the GABAC receptors and GABA.
The antiepileptic effect of pinellia total alkaloids(PTA) on penicillin(PNC) chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid(GABA) concentrations and the expression level of cerebral GABA_A receptor in hippocampus.The influence of PTA on epilepsy seizure latency and degree in PNC chronically kindled rats were observed.High performance liquid chromatography(HPLC) was adopted to measure the concentrations of Glu, Asp,Gly and GABA in hippocampus. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expression of cerebral GABAA receptor mRNA. Compared with normal rats, the levels of GABA and Gly decreased obviously while the level of Glu and Asp increased significantly in model rats. The cerebral GABAA receptor mRNA level was also decreased at the same time. The difference was statistically different compared to the control group. PTA could prolong the latent period of the penicillin induced seizure and weaken the extent of seizure, compared with the model group without PTA treatment. Moreover, PTA increased the level of GABA and the expression level of GABAA receptor, while decreased the level of Glu significantly. However, it had no obvious effect on the level of Gly and Asp. Pre-treatment of PTA can also increase the GABAA receptor mRNA level. In conclusion, PTA could alleviate the PNC chronically kindled rat seizure. It increased the GABA level and the expression of GABAA receptor, and it decreased the Glu concentration.