Kindling antagonism: effects of norepinephrine depletion on kindled seizure suppression after concurrent, alternate stimulation in rats.

The concurrent, alternate electrical stimulation of the entorhinal cortex and septal nucleus results in the development of fully generalized seizures at one electrode site and the suppression of seizure development at the other. We have labeled this phenomenon kindling antagonism. Selective, whole-brain depletion of norepinephrine (NE) virtually eliminates the development of kindling antagonism such that fully generalized seizures develop at both sites in a majority of animals. This effect occurs in the absence of appreciable changes in kindling characteristics of these animals compared with either untreated or vehicle-treated controls. These results suggest that the suppression of seizure development observed in the kindling antagonism model is normally maintained by a NE-dependent mechanism. Our results support those of earlier studies using single-site kindling paradigms in which NE depletion facilitates the rate of kindled seizure development. We suggest that the NE-dependent mechanism responsible for the seizure suppression observed to follow concurrent, alternate stimulation and the suppression of seizure development using single-site kindling paradigms may be the same. The nature of this NE-dependent seizure suppression mechanism and the anatomic locus or loci critical for this effect remain questions for future research.