This project uses electrophysiological and biochemical methods to study a new model of status epilepticus. This model uses pretreatment with lithium followed by administration of subthreshold doses of convulsants. The basic model entails treatment with LiCl (3 mEq/kg; ip) and pilocarpine (30 mg/kg; sc) which invariably produces generalized convulsive status epilepticus which lasts for several hours and is fatal. There are three major goals of this proposal. (1) We will test the hypothesis that lithium lowers the seizure threshold to other convulsive stimuli, including ECS, bicuculline, picrotoxin, pentylenetetrazole, kainic acid and chemical (carbachol) and electrical kindling. (2) We will test the hypothesis that function of the GABAergic system is impaired during status epilepticus by measuring the state of the GABA/benzodiazepine/picrotoxin chloride channel complex during seizures. (3) We will test the hypothesis that alteration of calcium homeostatis plays a role in status epilepticus by testing the anticonvulsant and proconvulsant actions of calcium antagonists and a calcium agonist, respectively, and the effects of seizures and drug treatments on calcium homeostasis in synaptosomes.
