THE ALPHA(2)-ADRENOCEPTOR AGONIST CLONIDINE SUPPRESSES SEIZURES, WHEREAS THE ALPHA(2)-ADRENOCEPTOR ANTAGONIST IDAZOXAN PROMOTES SEIZURES INAMYGDALA-KINDLED KITTENS - A COMPARISON OF AMYGDALA AND PONTINE MICROINFUSION EFFECTS

Purpose: We sought to determine whether local, in vivo microinfusion o f an alpha(2)-adrenoreceptor agonist and antagonist into either the am ygdala or the pens (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 t he same protocol, in which the amygdala microinfusion paradigm precede d the pontine microinfusion series. Microinfusions (1 mu l) of the alp ha(2)-agonist clonidine (CLON) and of the alpha(2)-antagonist idazoxan (IDA) were made over 1 min through cannulas adjacent to stimulating e lectrodes in the kindled amygdala or through cannulas adjacent to reco rding electrodes in the ipsilateral LC. Order of administered drugs (C LON vs. IDA) and dosages (n = 3 each) was partly counterbalanced. Foca l and convulsive seizure thresholds were evaluated 10-12 min postinfus ion and compared to thresholds obtained during two interspersed contro l conditions (vehicle control = 1 mu l microinfusion of sterile saline ; sham control = needle insertion only), Results: CLON significantly i ncreased focal and generalized seizure thresholds, whereas IDA signifi cantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose dependent and more potent after pontine than amyg dala microinfusion. Conclusions: Our results confirm and extent findin gs of previous researchers who used unlocalized in vivo manipulations to show that norepinephrine (NE) is a highly antiepileptic agent in th e amygdala kindling preparation. With further investigation, the resul ts may ultimately lead to development of microinfusion techniques as a n alternative treatment option for limbic epilepsy.