Turski W A, Cavalheiro E A, Turski L, Kleinrok Z
Behav Brain Res. 1983 Mar;7(3):361-70. doi: 10.1016/0166-4328(83)90026-8.
Unilateral microinjections of bethanechol chloride into the CA3 subfield of the dorsal hippocampus in unrestrained rats produced a seizure-related type behavioural and disseminated brain damage syndrome. Injection of bethanechol in the dose of 50 micrograms resulted in locomotor activation, mouth movements, teeth chattering, chewing, wet dog shakes and mild limbic seizures. Shortly after intrahippocampal injection the electroencephalogram (EEG) showed an increase in the frequency of the theta rhythm in both hippocampi. Then EEG showed spiking activity of high frequency in the injected hippocampus, with rapid propagation to the lateral septum, amygdala, neocortex and contralateral hippocampus. The periods of spiking activity of high frequency were followed by depression in the background EEG rhythm with some interspersed spike and wave complexes of very low frequency. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. The patterning of distant damage after intrahippocampal injections of bethanechol involved the piriform cortex, entorhinal cortex, olfactory tubercle, anterior olfactory nucleus, subiculum, amygdaloid complex, temporoparietal cortex and hypothalamic nuclei. Neuropathological alterations were occasionally observed in the lateral septum and thalamus. These results seem to establish a causative relationship between excessive stimulation of cholinergic muscarinic receptors in the hippocampal formation and epileptic brain damage.
在未受约束的大鼠中，向背侧海马体的CA3亚区单侧微量注射氯化氨甲酰甲胆碱会产生与癫痫相关的行为类型和弥漫性脑损伤综合征。注射50微克剂量的氯化氨甲酰甲胆碱会导致运动激活、口部运动、牙齿打颤、咀嚼、湿狗样抖动和轻度边缘性癫痫发作。海马体内注射后不久，脑电图（EEG）显示双侧海马体中θ节律的频率增加。然后脑电图显示注射侧海马体出现高频棘波活动，并迅速传播至外侧隔区、杏仁核、新皮层和对侧海马体。高频棘波活动期之后是背景脑电图节律的抑制，并伴有一些非常低频的散在棘波和慢波复合波。额叶前脑切片的组织学检查显示出弥漫性、明显由癫痫介导的脑损伤模式。海马体内注射氯化氨甲酰甲胆碱后远处损伤的模式涉及梨状皮质、内嗅皮质、嗅结节、前嗅核、海马下托、杏仁复合体、颞顶叶皮质和下丘脑核。偶尔在外侧隔区和丘脑观察到神经病理改变。这些结果似乎确立了海马结构中胆碱能毒蕈碱受体的过度刺激与癫痫性脑损伤之间的因果关系。
