Ormandy G C, Song L, Jope R S
Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.
Exp Neurol. 1991 Mar;111(3):356-61. doi: 10.1016/0014-4886(91)90103-j.
Lithium pretreatment of rats has previously been shown to potentiate the convulsant effects of cholinomimetic drugs, such as pilocarpine. The first objective of this project was to determine if lithium also potentiates seizures induced by other classes of drugs. Lithium pretreatment of rats did not affect seizure activity induced by administration of N-methyl-D-aspartate, kainic acid, bicuculline, or pentylenetetrazole. This suggests that the proconvulsant effect of lithium is largely selective for cholinomimetics. A second series of experiments investigated possible mechanisms of the lithium potentiation of pilocarpine-induced seizures. The alpha 2-adrenergic receptor agonist clonidine suppressed seizure development, and the antagonist idazoxan enhanced the onset of seizures, suggesting that endogenous norepinephrine provides anticonvulsant properties. Administration of the norepinephrine depleter DSP-4 potentiated pilocarpine-induced seizures. These results suggest that the previously reported impairment of noradrenergic function by lithium may play a role in its potentiation of cholinomimetic-induced seizures.
先前的研究表明，对大鼠进行锂预处理可增强拟胆碱药物（如毛果芸香碱）的惊厥作用。本项目的首要目标是确定锂是否也会增强其他类药物诱发的癫痫发作。对大鼠进行锂预处理并未影响由N-甲基-D-天冬氨酸、 kainic酸、荷包牡丹碱或戊四氮给药诱发的癫痫活动。这表明锂的促惊厥作用在很大程度上对拟胆碱药物具有选择性。第二系列实验研究了锂增强毛果芸香碱诱发癫痫发作的可能机制。α2-肾上腺素能受体激动剂可乐定抑制癫痫发作的发展，而拮抗剂咪唑克生则增强癫痫发作的起始，这表明内源性去甲肾上腺素具有抗惊厥特性。去甲肾上腺素耗竭剂DSP-4的给药增强了毛果芸香碱诱发的癫痫发作。这些结果表明，先前报道的锂对去甲肾上腺素能功能的损害可能在其增强拟胆碱药物诱发癫痫发作中起作用。
