REPEATED GENERALIZED SEIZURES INDUCE TIME-DEPENDENT CHANGES IN THE BEHAVIORAL SEIZURE RESPONSE INDEPENDENT OF CONTINUED SEIZURE INDUCTION

This study examined both the acute and long-lasting changes in seizure susceptibility that occur in response to the repeated induction of ge neralized seizure activity. Daily flurothyl-induced generalized clonic seizures resulted in a progressive decrease in both the generalized s eizure threshold and the latency to the first myoclonic jerk. The thre shold reduction was significant as early as the second trial and was m aximal by trial 5. However, a minimum of eight seizures was necessary for the maximal reduction to be long-lasting. The present study also e xamined the effects of the number of seizures and the duration of the stimulation-free interval on the type of generalized seizure expressed . During the induction phase of the experiment, only generalized cloni c seizures (''forebrain seizures'') were expressed. If, however, the a nimal was retested after a 1, 2, 3, or 4 week stimulation-free interva l, a progressive increase in both the proportion of animals expressing ''brainstem seizure'' behaviors and the median seizure score was obse rved. The progression of flurothyl-induced generalized seizure behavio rs was significantly altered if (1) a minimum of eight generalized clo nic seizures had been expressed, and (2) a minimum of a 2 week stimula tion-free interval followed. Fewer generalized clonic seizures failed to reliably produce changes in seizure phenotype, even after extended stimulus-free intervals. These data indicate that specific kindling pr ocesses are initiated during the interval of repeated seizure inductio n and evolve in the absence of continued seizure induction. Furthermor e, these mechanisms of epileptogenesis were found to be manifest predo minantly as a change in the seizure phenotype expressed and to proceed independent of changes in the generalized seizure threshold.