McCown T J, Givens B S, Breese G R
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill.
J Pharmacol Exp Ther. 1987 Nov;243(2):603-8.
Using a model in which seizure activity was elicited electrically from the inferior colliculus, the influence of both inhibitory and excitatory putative neurotransmitter amino acids on this seizure activity was assessed by manipulating neurotransmitter amino acid function. It was found that i.c.v. administration of the inhibitory amino acids taurine (2.5 micrograms) or glycine (30 micrograms), or the gamma-aminobutyric acidA agonist, muscimol (300 ng), significantly elevated the threshold current necessary to initiate seizure activity from the inferior collicular cortex. Similarly, the microinjection of muscimol (10 or 30 ng) or racemic baclofen (20 or 60 ng), a gamma-aminobutyric acidB agonist, into the inferior collicular cortex significantly elevated the seizure threshold current, but inferior collicular microinjections of taurine (1 microgram) or glycine (1 microgram) exerted no effect on the seizure threshold current. When excitatory amino acid influences were assessed on seizure production, neither ventricular administration of glutamate or aspartate (100 micrograms) nor inferior collicular administration of glutamate (1 or 10 micrograms) or aspartate (10 micrograms) changed the seizure initiation threshold. Although the site administration of 30 or 100 ng of N-methyl-D-aspartic acid did not alter the seizure initiation threshold, 300 ng of N-methyl-D-aspartic acid significantly lowered the amount of electrical stimulation necessary to elicit the seizure activity. Conversely, blockade of N-methyl-D-aspartic acid receptors in the inferior colliculus with L-3-amino-7-phosphonoheptanoic acid (100 ng) or gamma-glutamylglycine (200 ng) significantly elevated the threshold current for seizure production, whereas microinjection of DL-3-amino-phosphonobutyric acid (200 ng) or glutamic acid diethyl ester (1 microgram) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
使用一种通过电刺激下丘诱发癫痫活动的模型,通过操纵神经递质氨基酸功能来评估抑制性和兴奋性假定神经递质氨基酸对这种癫痫活动的影响。结果发现,脑室内注射抑制性氨基酸牛磺酸(2.5微克)或甘氨酸(30微克),或γ-氨基丁酸A激动剂蝇蕈醇(300纳克),可显著提高从下丘皮质引发癫痫活动所需的阈值电流。同样,向下丘皮质微量注射蝇蕈醇(10或30纳克)或γ-氨基丁酸B激动剂消旋巴氯芬(20或60纳克),可显著提高癫痫阈值电流,但向下丘微量注射牛磺酸(1微克)或甘氨酸(1微克)对癫痫阈值电流无影响。当评估兴奋性氨基酸对癫痫发作的影响时,脑室内注射谷氨酸或天冬氨酸(100微克)以及向下丘注射谷氨酸(1或10微克)或天冬氨酸(10微克)均未改变癫痫发作起始阈值。尽管注射30或100纳克N-甲基-D-天冬氨酸对癫痫发作起始阈值无影响,但300纳克N-甲基-D-天冬氨酸可显著降低引发癫痫活动所需的电刺激量。相反,用L-3-氨基-7-膦酰庚酸(100纳克)或γ-谷氨酰甘氨酸(200纳克)阻断下丘中的N-甲基-D-天冬氨酸受体,可显著提高癫痫发作的阈值电流,而微量注射DL-3-氨基膦酸丁酸(200纳克)或谷氨酸二乙酯(1微克)则无影响。(摘要截选至250词)