Development of kindling-prone and kindling-resistant rats: selective breeding and electrophysiological studies

Because of the growing need for an animal model of complex partial seizures based on a genetic predisposition, we combined the kindling model of epilepsy with selective-breeding procedures to develop two new lines (or strains) of rats that are kindling-prone or kindling-resistant. The selection of these strains was based on their rates of amygdala kindling. From a parent population of Long Evans hooded and Wistar rats, the males and females that showed the fastest and slowest amygdala kindling rates were selected and bred. Similar selection procedures continued through F11, although there was little or no overlap in the distribution of kindling rates for the two new strains (FAST and SLOW) by F6. Examination of both local and propagating seizure profiles of the new strains from F6 to F10 revealed that the FAST and SLOW rats had similar amygdala afterdischarge (AD) thresholds and associated AD durations. Also, the convulsion profiles of the stage-5 responses were similar, although the severity was greater in the FAST rats. Clearly the selection was not based on local mechanisms controlling the threshold for amygdala AD evocation, but rather for the spread of AD from the focus and the recruitment of other structures, ultimately triggering convulsive seizures. Although evoked potentials and potentiation effects were similar between the strains, the SLOW rats showed a greater paired-pulse depression, raising the possibility that they differ in inhibitory mechanisms. The specificity of strain differences for the amygdala and its associated networks is described in our accompanying paper (McIntyre et al., 1999. FAST and SLOW amygdala kindling rat strains: Comparison of amygdala, hippocampal, piriform and perirhinal cortex kindling. Epilepsy Res. 35, 197-209). These strains should provide many clues to the dispositional differences between individuals for the development of epilepsy originating in temporal lobe structures.