Shin Rick S, McIntyre Dan C
Institute of Neuroscience, Department of Psychology, Life Sciences Research Building, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
Neuropharmacology. 2007 Feb;52(2):321-32. doi: 10.1016/j.neuropharm.2006.08.004. Epub 2006 Oct 5.
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.
在对杏仁核点燃易发作（快速型）或抗发作（缓慢型）的大鼠进行选择性培育后，研究了α(2)去甲肾上腺素能受体在杏仁核“密集”刺激（MS）过程中的参与情况。在MS过程中腹腔注射选择性α(2)去甲肾上腺素能激动剂胍法辛或拮抗剂咪唑克生，以研究后续放电后（AD）阈值、AD持续时间和行为性癫痫发作表现的变化。在MS治疗后2周内，每周再次评估这些测量指标。此后立即开始每日点燃。在经历6次每日1次的5期惊厥性癫痫发作后，再次给予胍法辛或咪唑克生。使用咪唑克生时，与MS治疗期间的胍法辛或生理盐水对照组相比，缓慢型大鼠表现出更多的惊厥性癫痫发作次数和更长的AD持续时间。快速型大鼠不存在咪唑克生的这种促惊厥特性。相比之下，在胍法辛存在的情况下，快速型大鼠表现出增强的惊厥表达。在完全点燃的大鼠中，咪唑克生和胍法辛对缓慢型大鼠的癫痫发作持续时间和严重程度有不同影响，但对快速型大鼠则没有。这些数据表明，快速型和缓慢型大鼠α(2)去甲肾上腺素能系统的某些方面存在差异，这些受体控制癫痫发作发生和传播的机制可能受遗传控制且各不相同。
