ROLE OF GABA IN THE GENESIS OF CHEMOCONVULSANT SEIZURES

The direct or indirect interference with GABA-mediated neurotransmission results in convulsive seizure activity in humans and experimental animals. When this convulsant effect is experimentally analyzed, it turns out to be a product of discrete and restricted cerebral sites of drug action. Depending upon the brain circuitry affected, different convulsant patterns are produced. Acute interference with GABA transmission in convulsant trigger sites in the forebrain evokes convulsant seizures which can be clearly distinguished from those evoked by interference with GABA transmission in the hindbrain convulsant sites. While acute alterations of forebrain seizure susceptibility do not change hindbrain seizure susceptibility, chronic or repeated exposure to seizures may cause simultaneous ''kindling'' of both systems. In addition to the specific convulsant sites of action of GABA antagonists in the brain there are specific sites where GABA antagonists exert an anticonvulsant action. The ability of a chemical agent to evoke a convulsive seizure by interfering with GABA transmission depends upon the relative effect of the agent on GABA transmission in different brain areas as well as its effect on other excitatory and inhibitory neurotransmitters with which GABA interacts.