Concurrent alternating stimulation of two limbic sites culminates in
typical kindling of generalized seizures from one site (dominant), whereas the
other site (suppressed) supports only nongeneralized seizures for as long as
stimulation of the dominant site continues (kindling antagonism). Burchfiel
and Applegate (1989; 1990) claimed that antagonism reflects a frank arrest
of kindling from the suppressed site at an intermediate stage. They argued,
moreover, that the eventual generalization of seizures provoked from the
suppressed site after the termination of stimulation of the dominant site
reflects a resumption of kindling from its previous state of arrest.
Burchfiel and Applegate also claimed that the behaviorally stereotyped
arrest of kindling from the suppressed site reveals critical transitions
between sequentially expressed mechanisms that govern both antagonism
and kindling. They therefore viewed kindling as a stepwise process that is
mediated by qualitatively and temporally distinct mechanisms. This position
hinges on the assumption that antagonism reflects a true arrest of kindling
from the suppressed site rather than a transient inhibition of seizures. I
conducted the following experiments to determine whether the assumption
is justified,
In Experiment 1, I replicated and extended the observations of
Burchfiel and Applegate concerning the expression of antagonism during
alternating stimulation of limbic as well as nonlimbic sites. The results of
Experiment 1 thus indicate that antagonism is indeed a robust phenomenon
and therefore worthy of further study.
In Experiment 2, the imposition of a prolonged stimulation-free period
(30 d) after the termination of stimulation of the dominant site (amygdala)
did not significantly reduce the number of stimulations of the suppressed
site (septal area) required to elicit a generalized seizure. Also, epileptiform
after discharge provoked from the septal area increased during alternating
stimulation, and the septal area supported generalized seizures after fewer
stimulations in rats previously expressing antagonism as compared to control
rats previously kindled from the amygdala. Collectively, these data are
consistent with the view of Burchfiel and Applegate that kindling from the
suppressed site progresses to an intermediate stage during alternating
stimulation and resumes after the termination of stimulation of the dominant
site.
The results of Experiment 2 also suggest the possibility that the
development of seizures from the suppressed site after the termination of
stimulation of the dominant site is dictated by the additive expression of:
first, the well-documented facilitation of kindling from one site that reliably
follows kindling from another (i.e., transfer between the amygdala, which
supported generalized seizures, and the septal area); second, (partial)
kindling from the septal area, which previously supported nonconvulsive or
partial seizures, during the Initial Phase. The results of Experiment 3
revealed that the facilitation of seizure development from the septal area
observed in rats previously exposed to alternating stimulation, which
perhaps is attributable to partial kindling from the suppressed site, was site specific.
Rats subjected to alternating stimulation of the left amygdala and
right septal area and control rats previously stimulated only in the left
amygdala subsequently demonstrated generalized seizures following similar
numbers of stimulations of the previously unstimulated right amygdala.
Another plausible view is that antagonism reflects a long-lasting (>
30 d) form of inhibition that is perhaps uniquely invoked by alternating
stimulation, While the results of Experiments 1 - 3 do not rule out this
possibility, the results of Experiment 4 clearly indicate that the persistence
of any such effects of alternating stimulation is not mediated by continuing
influences of the dominant site: After the establishment of antagonism,
radio-frequency lesions of the dominant site (amygdala) failed to alter the
development of seizures provoked by stimulation of the suppressed site
(septal area). / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/9649 |
| Date | 09 July 2018 |
| Creators | Kirkby, Robert Duncan |
| Contributors | Corcoran, Michael |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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