Myslobodsky M S, Valenstein E S
Epilepsia. 1980 Apr;21(2):163-75. doi: 10.1111/j.1528-1157.1980.tb04058.x.
The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long-Evans rats. The newly synthesized GABA-transaminase inhibitor, gamma-acetylenic GABA (GAG) administered on four consecutive days (100 mg/kg, followed by 50 mg/kg, i.p.) was found to either significantly reduce, or eliminate entirely, the behavioral seizures normally produced by amygdala stimulation. The effect is seen after the first injection of GAG although its magnitude was greater on subsequent days. Behavioral seizures reappeared 2 to 3 days after termination of GAG treatment. The duration of electrographic seizures (self-sustained amygdala after discharge) was either unchanged or greater on the first day of GAG treatment, but was briefer on subsequent days. The duration of afterdischarges returned to normal levels 1 to 2 days earlier than the behavioral seizures after the termination of GAG. Picrotoxin (1.5-2 mg/kg, i.p.) did not antagonize either electrographic or behavioral effects of inhibition produced with GAG. Electrical stimulation of amygdala delivered during the initial sedation stage induced by picrotoxin resulted in further regression of kindled seizures in the majority of animals. Although in doses employed, GAG alleviates amygdaloid-kindled seizures its use requires caution in view of its ability to reduce arousal level.
在Long-Evans大鼠中研究了脑内γ-氨基丁酸(GABA)水平升高对完全点燃的杏仁核癫痫发作的影响。连续四天给予新合成的GABA转氨酶抑制剂γ-乙炔基GABA(GAG)(100mg/kg,随后50mg/kg,腹腔注射),发现其可显著减轻或完全消除杏仁核刺激通常所引发的行为性癫痫发作。首次注射GAG后即可观察到这种效果,不过在随后几天效果更为明显。GAG治疗终止后2至3天,行为性癫痫发作再次出现。在GAG治疗的第一天,脑电图癫痫发作(自持续的杏仁核放电后)的持续时间要么未变,要么延长,但在随后几天则缩短。放电后持续时间在GAG治疗终止后比行为性癫痫发作提前1至2天恢复到正常水平。印防己毒素(1.5 - 2mg/kg,腹腔注射)并未拮抗GAG所产生的脑电图或行为抑制效应。在印防己毒素诱导的初始镇静阶段对杏仁核进行电刺激,在大多数动物中导致点燃癫痫发作进一步消退。尽管在所使用的剂量下,GAG可减轻杏仁核点燃的癫痫发作,但鉴于其降低觉醒水平的能力,使用时需谨慎。