Secondary epileptogenesis in frog forebrain: effect of inhibition of protein synthesis.

Secondary epileptogenesis was induced in the hippocampal cortex of the paralyzed bullfrog by means of localized, unilateral, intermittent electrical stimulation (kindling). Stimuli were designed to yield a brief but definite after-discharge. In control animals a progressive increase in after-discharge duration occurred at the 1 degree (stimulated) site and then at the 2 degrees site (contralateral hippocampus). Spontaneous epileptiform potentials (SEP's) occurred between stimuli, eventually independently on both sides. Cycloheximide (50 mg/kg) caused 88-99% reduction in protein synthesis, measured by 14C-leucine incorporation into brain protein. Cycloheximide-treated animals revealed no evidence of progressive prolongation of after-discharge duration when subjected to the kindling procedure (p = 0.1205 X 10(-7)). SEP's were reduced in the cycloheximide-treated animals, and confined to 1 degree hemisphere (p = 0.6 X 10(-10)). Since cycloheximide did not disturb normal electrogenesis or disrupt the after-discharges, this experiment distinguishes processes dependent upon electrical events from those requiring macromolecular synthesis. Protein synthesis seems critical to the emergence of spontaneous and autonomous epileptiform behavior of neural aggregates.