脑室内注射4-氨基吡啶诱发家兔惊厥

家兔icv 4-氨基吡啶(4-AP)8μg能诱发反复发作的惊厥,ECoG呈现高幅棘波。抗癫痫药苯妥英钠、苯巴比妥钠、安定均能有效控制4-AP诱发的惊厥,使ECoG棘波消失。丙戊酸钠也有一定效果。东莨菪碱、氟哌啶醇与酚妥拉明均能拮抗4-AP引起的惊厥。结果提示,4-AP诱发的惊厥可能与它促进中枢ACh;DA及NE等递质的释放有关。家兔icv 4-AP诱发的惊厥与常用的癫痫模型比较,有一定优点,可作为筛选抗癫痫药的动物模型之一。

INTRACEREBRAL-VENTRICULAR INJECTION OF 4-AMINOPYRIDINE INDUCED CONVULSION IN RABBITS

Intracerebral- ventricular (icv) injection of 4- aminopyridine (4-AP) 8 μg to rabbits generated convulsions and epileptic discharges in electrocorticogram (ECoG). With 40 rabbits, the occurrence of convulsion at this dose level was 100%. The results from five rabbits showed that seizures may break out repeatedly at intervals of 1～5 min and such state may last about 1.5 h. Antiepileptic drugs, such as phenytoin sodium, phenobarbital sodium and diazepam, were found to effectively control the seizures provoked by icy 4-AP. Sodium valproate was less effective than the foregoing drugs. The icv 4-AP-induced convulsion appeared to have some merits as compared with the old epilepsy models, such as those induced by electric stimulation, cardiazol, or icv ferrous sulfate. We feel that it may be recommended as a model for the preliminary screening of antiepileptic drugs.The seizures provoked by icv 4-AP were shown to be antagonized by scopolamine, haloperidol, phentolamine, or propranolol, but potentiated by l-dopa. It is now recognized that 4-AP can enhance the release of ACh, DA, and NE in the central nervous system. The present results suggest that the convulsion elicited by 4-AP seems to be related to the disturbance of synaptic transmission in the brain.