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 epile psy with selective-breeding procedures to develop two new lines (or strains ) of rats that are kindling-prone or kindling-resistant. The selection of t hese strains was based on their rates of amygdala kindling. From a parent p opulation of Long Evans hooded and Wistar rats, the males and females that showed the fastest and slowest amygdala kindling rates were selected and br ed. 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 se izure profiles of the new strains from F6 to F10 revealed that the FAST and SLOW rats had similar amygdala afterdischarge (AD) thresholds and associat ed AD durations. Also, the convulsion profiles of the stage-5 responses wer e similar, although the severity was greater in the FAST rats. Clearly the selection was not based on local mechanisms controlling the threshold for a mygdala AD evocation, but rather for the spread of AD from the focus and th e recruitment of other structures, ultimately triggering convulsive seizure s. Although evoked potentials and potentiation effects were similar between the strains, the SLOW rats showed a greater paired-pulse depression, raisi ng the possibility that they differ in inhibitory mechanisms. The specifici ty of strain differences for the amygdala and its associated networks is de scribed in our accompanying paper (McIntyre et al., 1999. FAST and SLOW amy gdala kindling rat strains: Comparison of amygdala, hippocampal, piriform a nd perirhinal cortex kindling. Epilepsy Res. 35, 197-209). These strains sh ould provide many clues to the dispositional differences between individual s for the development of epilepsy originating in temporal lobe structures. (C) 1999 Elsevier Science B.V. All rights reserved.