The alpha 2-adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2-adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens: a comparison of amygdala and pontine microinfusion effects.
OBJECTIVE
We sought to determine whether local, in vivo microinfusion of an alpha 2-adrenoreceptor agonist and antagonist into either the amygdala or the pons (locus ceruleus, LC) would have contrasting effects on evoked amygdala-kindled seizure susceptibility.


METHODS
The study population consisted of 6 amygdala-kindled kittens, each undergoing the same protocol, in which the amygdala microinfusion paradigm preceded the pontine microinfusion series. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulas adjacent to stimulating electrodes in the kindled amygdala or through cannulas adjacent to recording electrodes in the ipsilateral LC. 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 postinfusion and compared to thresholds obtained during two interspersed control conditions (vehicle control = 1 microliter microinfusion of sterile saline; sham control = needle insertion only).


RESULTS
CLON significantly increased focal and generalized seizure thresholds, whereas IDA significantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose dependent and more potent after pontine than amygdala microinfusion.


CONCLUSIONS
Our results confirm and extent findings of previous researchers who used unlocalized in vivo manipulations to show that norepinephrine (NE) is a highly antiepileptic agent in the amygdala kindling preparation. With further investigation, the results may ultimately lead to development of microinfusion techniques as an alternative treatment option for limbic epilepsy.
Shouse
M N
MN
VAMC Sepulveda, California, USA.
Langer
J
J
Bier
M
M
Farber
P R
PR
Alcalde
O
O
Moghimi
R
R
Richkind
M
M
Szymusiak
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology*; D004198:Disease Susceptibility / Q000139:chemically induced / Q000209:etiology; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D013238:Stereotaxic Techniques
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan