Anticonvulsant action of phenobarbital, diazepam, carbamazepine, and diphenylhydantoin in the electroshock test in mice after lesion of hippocampal pyramidal cells with intracerebroventricular kainic acid.

The electroshock test-taking hind limb tonic extension as the end point-was carried out on the fifth day after the intracerebroventricular injections of kainic acid (KA; 0.2 microgram per mouse). The following antiepileptics were tested for the anticonvulsant effects both in naive and KA-lesioned mice: phenobarbital (20 mg/kg), diazepam (8 mg/kg), carbamazepine (15 mg/kg) and diphenylhydantoin (10 mg/kg), all drugs being injected intraperitoneally 60 min before electroconvulsions. It was found that the protective effects of phenobarbital and diazepam were distinctly reduced in KA-lesioned animals when compared to naive mice. However, both carbamazepine and diphenylhydantoin protected KA-injected and control animals to a similar degree. Further, intracerebroventricular injections of KA resulted in the substantial loss of pyramidal cells in the whole CA3 field of the hippocampus. It is suggested that the intact hippocampus is necessary for the development of the full anticonvulsant effects of phenobarbital and diazepam, whilst the site of action of carbamazepine and diphenylhydantoin is independent of the hippocampus.