GABA receptors, lipids, and gangliosides in cobalt epileptic focus.

The seizure state induced in the rat by cerebral cortical implantation of cobalt metal has been increasingly used to study a variety of neurochemical parameters. This experimental model of epilepsy affords the opportunity to study events prior to the development of seizures, during the period of intense seizure activity, and during the period when seizure activity has essentially terminated. The seizures that occur in this model are intermittent and paroxysmal and share many other similarities with human epilepsy. The crucial question with this model, and indeed with any experimental model of epilepsy, is whether the basic seizure-producing mechanism(s) is similar. This question remains to be answered. There have been studies that show that changes in certain neurochemical parameters parallel the onset, intensity, and decline of seizure activity in cobalt-epileptic animals. Although extremely interesting, by themselves they do not prove a cause-and-effect relationship. Such parallelism is more apparent in the case of GABA than in the cases of lipids and gangliosides. GABA and its synthetic enzyme, glutamic acid decarboxylase (GAD), are both at normal levels prior to the development of seizures, are significantly decreased during the period of seizures, and return toward control values at a time when seizures are no longer apparent. On the other hand, there is no change in postsynaptic GABA binding sites (Bmax) prior to seizures, a significant increase in Bmax during seizure activity, and a return toward normal by 21 days (when seizure activity has terminated). Studies that have been carried out on lipids and gangliosides in cobalt-induced epilepsy are not nearly as extensive nor are the results as positive as those that have been obtained in the case of GABA. They do, however, provide provocative findings that may well be related to the genesis of epilepsy.