Differential noradrenergic influence on seizure expression in genetically Fast and Slow kindling rat strains during massed trial stimulation of the amygdala.
The involvement of alpha(2) noradrenergic receptors during amygdala 'massed' stimulation (MS) was examined in rats that were selectively bred to be seizure-prone (Fast) or seizure-resistant (Slow) to amygdala kindling. The selective alpha(2) noradrenergic agonist guanfacine, or the antagonist idazoxan, was intraperitoneally injected during the MS procedure to study subsequent changes in afterdischarge (AD) threshold, AD duration and behavioral seizure expression. These measurements were again assessed weekly for 2 weeks after the MS treatment. Daily kindling began immediately thereafter. Following 6 stage-5 once daily convulsive seizures, guanfacine or idazoxan were re-administered. With idazoxan, the Slow rats expressed greater numbers of convulsive seizures and longer AD durations compared to guanfacine or saline controls during MS treatment. This pro-convulsive property of idazoxan was absent in Fast rats. By contrast, Fast rats showed enhanced convulsive expression in the presence of guanfacine. In the fully kindled rat, idazoxan and guanfacine differentially impacted seizure duration and severity in the Slow rats, but again not in the Fast rats. These data suggest that some aspect(s) of the alpha(2) noradrenergic system in the Fast and Slow rats are dissimilar and the mechanisms by which these receptors govern seizure genesis and propagation may be genetically controlled and distinct.
Shin
Rick S
RS
Institute of Neuroscience, Department of Psychology, Life Sciences Research Building, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
McIntyre
Dan C
DC
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology* / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000009:adverse effects; D016316:Guanfacine / Q000008:administration & dosage; D019329:Idazoxan / Q000008:administration & dosage; D007696:Kindling, Neurologic / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D016316:Guanfacine; D009638:Norepinephrine; D019329:Idazoxan