Wahnschaffe U, Löscher W
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, F.R.G.
Eur J Pharmacol. 1990 Sep 21;186(2-3):157-67. doi: 10.1016/0014-2999(90)90429-a.
The substantia nigra (SN) is thought to be involved in the regulation of seizure activity and there is evidence that the nigra might be a site of anticonvulsant drug action, especially in the case of drugs that act by potentiating gamma-aminobutyric acid (GABA)-mediated neurotransmission. The current studies monitored the anticonvulsant effect of four major antiepileptic drugs, i.e. valproic acid, carbamazepine, phenobarbital and diazepam, in fully kindled rats before and after bilateral destruction of the SN. Rats were kindled by stimulation of either the basolateral amygdala or the piriform cortex. The SN was lesioned bilaterally by microinjection of ibotenic acid, and only animals with near-complete, selective destruction of the SN were used for final evaluation of the anticonvulsant drug experiments. The behavioural characteristics and the duration of fully kindled seizures were not altered by bilateral destruction of the SN. Phenobarbital, diazepam and valproate significantly reduced kindled seizures severity and duration before and after the SN lesions. Carbamazepine was the only drug to show a marked decrease in its anticonvulsant effects after SN lesion. Since benzodiazepines, valproate and phenobarbital are though to enhance GABAergic transmission, the lack of effect of SN lesions on the anticonvulsant effects of these drugs argues against the suggestion that the SN is the anatomical site responsible for exerting anticonvulsant effects in response to drug-induced augmentation of GABA transmission.
黑质（SN）被认为参与癫痫活动的调节，并且有证据表明黑质可能是抗惊厥药物作用的部位，特别是对于通过增强γ-氨基丁酸（GABA）介导的神经传递起作用的药物。目前的研究监测了四种主要抗癫痫药物，即丙戊酸、卡马西平、苯巴比妥和地西泮，在双侧损毁SN前后对完全点燃大鼠的抗惊厥作用。大鼠通过刺激基底外侧杏仁核或梨状皮质被点燃。通过微量注射鹅膏蕈氨酸双侧损毁SN，只有SN几乎完全被选择性损毁的动物才用于抗惊厥药物实验的最终评估。双侧损毁SN并未改变完全点燃癫痫发作的行为特征和持续时间。苯巴比妥、地西泮和丙戊酸盐在SN损毁前后均显著降低了点燃癫痫发作的严重程度和持续时间。卡马西平是唯一一种在SN损毁后抗惊厥作用显著降低的药物。由于苯二氮䓬类、丙戊酸盐和苯巴比妥被认为可增强GABA能传递，SN损毁对这些药物抗惊厥作用无影响，这与SN是响应药物诱导的GABA传递增强而发挥抗惊厥作用的解剖学部位这一观点相悖。
