Extrafocal threshold reductions in amygdala-kindled rats.

Purpose: Racine's classic study suggested that after discharge thresholds were reduced in the primary stimulation site (amygdala) of kindled rats, but that that they were not reduced in secondary (nonstimulated) sites. However, recent reports of neurochemical changes related to excitation and inhibition in nonstimulated sites in kindled brains would be expected to cause reductions in afterdischarge thresholds in these sites. More recently Sanei et al. have reported a significant threshold reduction in the piriform cortex of amygdala- and hippocampus-kindled cats, but not in the entorhinal cortex. The present study was designed to determine whether the results of Sanei et al. in cats could be replicated in rats kindled in the amygdala-a model commonly used in studies of seizure mechanisms and anticonvulsant drug development.

Methods: Adult, male Long-Evans rats were kindled in the amygdala or given matched handling. Beginning 48 h following the last stimulation, afterdischarge thresholds were determined in the ipsilateral piriform and entorhinal cortices. Amygdala thresholds were determined 24 h later.

Results: Afterdischarge thresholds were significantly reduced in both the amygdala and the ipsilateral entorhinal cortex of amygdala-kindled rats. Afterdischarge thresholds in the piriform cortex did not differ significantly between kindled and control subjects.

Discussion: These data suggest that threshold reduction occurs outside the primary kindling site in rats as well as in cats. Extrafocal changes in afterdischarge threshold may be functionally important, and might possibly relate to extrafocal neurochemical changes and progressive generalization of seizure discharge from discrete focal sites.