PHARMACOLOGICAL AND BIOCHEMICAL STUDIES OF AMYGDALA KINDLING

本计画的目的是了解并调整课程 杏仁核的发育引发癫痫 的影响 卡马西平和其他抗惊厥药对杏仁核点燃的作用 检查与点燃癫痫发作发展阶段的关系（以及 点燃刺激的类型;见上文-药理学点燃）。 剂 与特定的生物靶系统已经被用来试图 调节卡马西平对点燃癫痫发作的抗惊厥作用， 以阐明卡马西平的作用机制。 最后， 关于杏仁核点燃的可能机制的研究已经 与Mike Clark、Jeff罗森、Russel Margolis和DeMaw博士一起进行 庄（BPB），和博士马克史密斯和菲尔黄金（CNE分支）。 迄今为止的重大发现包括以下方面的证明： 卡马西平是一种有效的抗惊厥药物，在完成 杏仁核点燃阶段，但不是在癫痫发作发展期间; 2） 丙戊酸是一种有效的抗惊厥剂， 发展和完成癫痫发作; 3）卡马西平的抗惊厥药 作用于外周型的药物可以逆转这种效应。 苯二氮卓受体（Ro 5 -4864）和α-2-去甲肾上腺素能受体 （育亨宾）; 4）杏仁核点燃癫痫发作，电休克 癫痫发作和杏仁核的后放电活动（没有 全身性癫痫发作）可以诱导CRH-mRNA在海马，在细胞 正常情况下不表达CRH信息; 5）嗅觉损害 灯泡不影响杏仁核点燃癫痫发作的发展， 对卡马西平、丙戊酸盐或地西泮的抗惊厥反应; 6） 点燃大鼠无癫痫发作产生抗惊厥药 在随后的测试中的不应性; 7）原癌基因c-fos是 在点燃发展过程中以区域选择性方式诱导， 在点燃的早期阶段，这取决于 引起的后放电持续时间;和8）TRH的mRNA也 随着杏仁核点燃而增加，在与c-fos大致相同的区域 表情

The objectives of this project are to understand and modulate the course of development of amygdala kindled seizures. The effects of carbamazepine and other anticonvulsants on amygdala kindling have been examined in relation to stage of kindled seizure development (as well as type of kindling stimulus; see above--pharmacological kindling). Agents with specific biological target systems have been used to attempt to modulate carbamazepine's anticonvulsant effects on kindled seizures, in order to elucidate carbamazepine's mechanisms of action. Finally, Studies addressing possible mechanisms of amygdala kindling have been conducted with Drs. Mike Clark, Jeff Rosen, Russel Margolis, and DeMaw Chuang (BPB), and Drs. Mark Smith and Phil Gold (CNE Branch). Significant findings to date include demonstration of the following: 1) carbamazepine is an effective anticonvulsant agent during the completed phase of amygdala kindling, but not during seizure development; 2) valproic acid is an effective anticonvulsant agent against both seizure development and completed seizures; 3) carbamazepine's anticonvulsant effects can be reversed by agents that act at the peripheral-type benzodiazepine receptor (Ro5-4864) and the alpha-2-noradrenergic receptor (yohimbine); 4) amygdala kindled seizures, electroconvulsive shock seizures, and afterdischarge activity in the amygdala (without generalized seizures) can induce CRH-mRNA in the hippocampus, in cells which do not normally express CRH message; 5) lesions of the olfactory bulb do not affect the development of amygdala kindled seizures or anticonvulsant responsivity to carbamazepine, valproate, or diazepam; 6) the absence of seizures in kindled rats produces anticonvulsant refractoriness upon subsequent testing; 7) the proto-oncogene c-fos is induced in a regionally selective manner during kindling development, which, in the early stages of kindling, is dependent upon the length of the elicited afterdischarge duration; and 8) the mRNA for TRH also increased with amygdala kindling, in roughly the same areas as the c-fos expression.