It has been reported previously that systemic administration of clonidine, an
agonist of α-2 receptors for noradrenaline, significantly retards amygdaloid kindling,
by delaying the emergence from partial seizure, Conversely, systemic administration
of α-2 antagonists has been reported to facilitate amygdaloid kindling, The
experiments I conducted attempted to discover whether α-2 adrenoceptors in the
amygdala participated in these effects, I examined the effect of either systemic
administration (i,p.) or intraamygdaloid infusions of a variety of noradrenergic drugs
on the kindling of seizures with electrical stimulation of the amygdala, Rats received
either low-frequency stimulation of the amygdala, to induce rapid kindling, or
conventional high-frequency stimulation, Drugs and electrical stimulation were
administered once every 48 hrs, I observed a significant retardation of kindling in
rats receiving i,p. injections of clonidine (0.1 mg/kg) or unilateral infusions of
clonidine in concentrations of [special characters omitted] to [special characters omitted] M, regardless of the stimulation frequency.
The prophylactic effect was due to a delay in the progression out of partial seizure. I observed similar effects with infusions of xylazine, also an α-2 adrenoceptor agonist,
The effect was specific to the amygdala/pyriform region, because infusions of
clonidine dorsal lo the amygdala were without effect. Power spectral analysis of the
AD from the stimulated and the contralateral amygdala during the initial occurrence
of bilateral AD failed to reveal differences attributable to clonidine, Therefore,
clonidine might retard kindling by modifying the propagation of AD from the
stimulated amygdala to a midbrain or pontine brainstem area critical, for the
expression of generalized seizures. Clonidine had no effect on established generalized
seizures, suggesting that it was producing a genuine prophylactic effect against
kindling. Unexpectedly, intraamygdaloid infusions of either idazoxan, yohimbine, or
SK&F 104856, antagonists of α-2 receptors, failed to accelerate kindling.
Simultaneous infusion of idazoxan blocked clonidine’s prophylactic effect, which
suggests strongly that this effect was mediated at the α-2 adrenoceptor. Blockade of
amygdaloid α-1 adrenoceptors with corynanthine failed to affect kindling.
I conclude that the population of α-2 adrenoceptors in the amygdala/pyriform
region contributes to the antiepileptogenic effect observed after systemic
administration of clonidine and that the facilitation of kindling observed after systemic
administration of α-2 antagonists reported previously may have been mediated by the
blockade of a population of α -2 adrenoceptors in addition to, or outside of, the
amygdala/pyriform region. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/9629 |
| Date | 06 July 2018 |
| Creators | Pelletier, Marc Roger |
| Contributors | Corcoran, M. E. |
| 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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