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This is the first report showing that local, in vivo microinfusion of alpha 2-adrenoreceptor agonists and antagonists have contrasting effects on amygdala-kindled seizure susceptibility. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and of the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulae adjacent to stimulating electrodes in five amygdala-kindled kittens. Order of administered drugs (CLON vs. IDA) and dosages (n = 3 each) was partly counterbalanced. Focal and convulsive seizure thresholds were evaluated 10-12 min post-infusion and compared to thresholds obtained during two, interspersed control conditions (vehicle control: 1 microliter microinfusion of sterile saline; sham control: needle insertion only). CLON significantly elevated focal and generalized seizure thresholds, whereas IDA significantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose-dependent. Results confirm and extend previous findings which employed unlocalized, in vivo manipulations to show that norepinephrine is a potent antiepileptic agent in the amygdala kindling preparation.
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