The alpha 2-agonist clonidine suppresses seizures, whereas the alpha 2-antagonist idazoxan promotes seizures--a microinfusion study in amygdala-kindled kittens.
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.
Shouse
M N
MN
VAMC, Sepulveda, CA 91343.
Bier
M
M
Langer
J
J
Alcalde
O
O
Richkind
M
M
Szymusiak
R
R
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology*; D004567:Electrodes, Implanted; D004594:Electrophysiology; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D019329:Idazoxan; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000927:Anticonvulsants; D003292:Convulsants; D004146:Dioxanes; D003000:Clonidine; D019329:Idazoxan