Jope R S, Gu X
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
Neurochem Res. 1991 Nov;16(11):1219-26. doi: 10.1007/BF00966699.
Seizures induced by three convulsant treatments produced differential effects on the concentration of acetylcholine in rat brain. Status epilepticus induced by (i) coadministration of lithium and pilocarpine caused massive increases in the concentration of acetylcholine in the cerebral cortex and hippocampus, (ii) a high dose of pilocarpine did not cause an increase of acetylcholine, and (iii) kainate increased acetylcholine, but the magnitude was lower than with the lithium/pilocarpine model. The finding that the acetylcholine concentration increases in two models of status epilepticus in the cortex and hippocampus is in direct contrast with many in vitro reports in which excessive stimulation causes depletion of acetylcholine. The concentration of choline increased during seizures with all three models. This is likely to be due to calcium- and agonist-induced activation of phospholipase C and/or D activity causing cleavage of choline-containing lipids. The excessive acetylcholine present during status epilepticus induced by lithium and pilocarpine was responsive to pharmacological manipulation. Atropine tended to decrease acetylcholine, similar to its effects in controls. The N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, reduced the excessive concentration of acetylcholine, especially in the cortex. Inhibition of choline uptake by hemicholinium-3 (HC-3) administered icv reduced the acetylcholine concentration in controls and when given to rats during status epilepticus. These results demonstrate that the rat brain concentrations of acetylcholine and choline can increase during status epilepticus. The accumulated acetylcholine was not in a static, inactive compartment, but was actively turning-over and was responsive to drug treatments. Excessive concentrations of acetylcholine and/or choline may play a role in seizure maintenance and in the neuronal damage and lethality associated with status epilepticus.
三种惊厥处理诱导的癫痫发作对大鼠脑内乙酰胆碱浓度产生了不同影响。（i）锂盐和毛果芸香碱联合给药诱导的癫痫持续状态导致大脑皮层和海马中乙酰胆碱浓度大幅升高；（ii）高剂量毛果芸香碱未引起乙酰胆碱增加；（iii）谷氨酸钾增加了乙酰胆碱，但增加幅度低于锂盐/毛果芸香碱模型。在皮层和海马的两种癫痫持续状态模型中乙酰胆碱浓度升高这一发现，与许多体外研究报告形成了直接对比，在这些报告中过度刺激会导致乙酰胆碱耗竭。在所有三种模型的癫痫发作过程中，胆碱浓度均升高。这可能是由于钙和激动剂诱导的磷脂酶C和/或D活性激活，导致含胆碱脂质的裂解。锂盐和毛果芸香碱诱导的癫痫持续状态期间存在的过量乙酰胆碱对药理操作有反应。阿托品倾向于降低乙酰胆碱，类似于其在对照组中的作用。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801降低了过量的乙酰胆碱浓度，尤其是在皮层中。脑室内注射半胱氨酸-3（HC-3）抑制胆碱摄取，降低了对照组以及癫痫持续状态大鼠体内的乙酰胆碱浓度。这些结果表明，在癫痫持续状态期间大鼠脑内乙酰胆碱和胆碱浓度会升高。积累的乙酰胆碱并非处于静态、无活性的隔室中，而是在积极周转，并且对药物治疗有反应。过量的乙酰胆碱和/或胆碱可能在癫痫维持以及与癫痫持续状态相关的神经元损伤和致死性中起作用。
