PHARMACOLOGICAL KINDLING

该项目的目标是研究和操纵 使用当地的 麻醉剂利多卡因和可卡因除此之外，其他 研究行为异常，包括行为刻板 可卡因、利多卡因攻击和可卡因相关死亡率 癫痫发作可卡因的点燃效应可能与其局部 麻醉特性，因为利多卡因具有类似的效果，但 与其他精神兴奋剂。局部麻醉的重要性 人类可卡因滥用的机制仍有待确定，但 可卡因相关的恐慌症（50%的可卡因使用者报告 呼叫可卡因热线）类似于点燃癫痫发作的发展， 提供了一个有趣的临床基础研究重叠。重大发现 该项目的主要内容包括：（1）发展当地 可以预防麻醉点燃癫痫发作及其相关的致死性， 慢性但非急性或反复急性卡马西平治疗; 2） 局部麻醉点燃癫痫发作模型可以提供一种新的方法， 研究卡马西平在情感性疾病中的作用机制， 也需要长期治疗; 3）压力相关肽 促肾上腺皮质激素释放激素（CRH）显著增强可卡因点燃 癫痫发作和致死性;和4）胆碱能机制可能是 重要参与局部麻醉癫痫发作， 利多卡因和可卡因点燃

The objectives of this project are to study and manipulate the course of development of pharmacologically kindled seizures using the local anesthetics lidocaine and cocaine. In addition to seizures, other behavioral abnormalities are studied, including behavioral stereotypies with cocaine, aggression with lidocaine, and mortality related to cocaine seizures. The kindling effects of cocaine are likely related to its local anesthetic properties, as similar effects are seen with lidocaine but not with other psychomotor stimulants. The importance of local anesthetic mechanisms in human cocaine abuse remains to be determined, but aspects of cocaine-related panic disorder (which is reported by 50% of cocaine users calling a cocaine hotline) resemble kindled seizure development and thus provide an intriguing clinical-basic research overlap. Significant findings of this project include the demonstration that 1) the development of local anesthetic kindled seizures and their associated lethality can be prevented with chronic, but not acute or repeated acute, carbamazepine treatment; 2) the local anesthetic kindled seizure model may offer a novel approach to examining carbamazepine's mechanisms of action in affective illness, which also requires chronic treatment; 3) the stress-related peptide corticotropin releasing hormone (CRH) markedly potentiates cocaine kindled seizure development and lethality; and 4) cholinergic mechanisms may be importantly involved in local anesthetic seizures and appear to differ for lidocaine and cocaine kindling.