Turski L, Cavalheiro E A, Turski W A, Meldrum B S
Neuroscience. 1986 May;18(1):61-77. doi: 10.1016/0306-4522(86)90179-x.
Seizures produced by pilocarpine given i.p. to rats provide an animal model for studying the initiation, spread and generalisation of convulsive activity within the forebrain. Pilocarpine, 380 mg/kg, produces a sequence of behavioural and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus, which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures. Microinjections of a selective antagonist at the N-methyl-D-aspartate receptor, (+/-)-2-amino-7-phosphonoheptanoate, into the substantia nigra pars reticulata, bilaterally, protects against the behavioural, electrographic and morphological features of seizures produced by pilocarpine, 380 mg/kg, with an ED50 of 0.0007 mumol (0.0004-0.0011). Microinjections of (+/-)-2-amino-7-phosphonoheptanoate, 0.005 or 0.01 mumol, into the substantia nigra pars compacta or into the dorsal part of mid-anterior striatum do not modify the electrographic and morphological sequelae of pilocarpine, 380 mg/kg. In rats pretreated with microinjections of N-methyl-D-aspartate into the substantia nigra pars reticulata, a non-convulsive dose of pilocarpine, 100 mg/kg, results in recurrent motor limbic seizures and status epilepticus. The ED50 of N-methyl-D-aspartate for the generation of seizures after pilocarpine, 100 mg/kg, is 0.0014 mumol (0.001-0.0019). Electrographic monitoring shows a pattern and sequence of evolution of convulsant activity within the hippocampus and cortex similar to that produced with pilocarpine, 380 mg/kg, alone. Morphological examination of brains from rats treated with N-methyl-D-aspartate in the substantia nigra pars reticulata and subsequently given pilocarpine, 100 mg/kg, which underwent status epilepticus, reveals widespread damage to the amygdala, thalamus, olfactory cortex, substantia nigra, neocortex, and hippocampus. Microinjections of N-methyl-D-aspartate, 0.002 mumol, into either the substantia nigra pars compacta or dorsal striatum, bilaterally, do not augment seizures produced by pilocarpine, 100 mg/kg. The results indicate that the threshold for pilocarpine-induced seizures in rats is modulated by excitatory amino acid neurotransmission within the substantia nigra pars reticulata.
腹腔注射毛果芸香碱诱导的大鼠癫痫发作可提供一种动物模型，用于研究前脑内惊厥活动的起始、扩散和泛化。380mg/kg的毛果芸香碱会引发一系列行为和脑电图改变，提示运动性边缘叶癫痫发作和癫痫持续状态，随后会导致边缘前脑广泛损伤，类似于长时间难治性癫痫发作后的损伤。双侧向黑质网状部微量注射N-甲基-D-天冬氨酸受体的选择性拮抗剂（±）-2-氨基-7-膦酰基庚酸，可预防380mg/kg毛果芸香碱所致癫痫发作的行为、脑电图和形态学特征，半数有效量（ED50）为0.0007μmol（0.0004 - 0.0011）。向黑质致密部或前纹状体背侧微量注射0.005或0.01μmol的（±）-2-氨基-7-膦酰基庚酸，不会改变380mg/kg毛果芸香碱所致癫痫发作的脑电图和形态学后遗症。在双侧黑质网状部微量注射N-甲基-D-天冬氨酸预处理的大鼠中，100mg/kg的非惊厥剂量毛果芸香碱会导致反复的运动性边缘叶癫痫发作和癫痫持续状态。100mg/kg毛果芸香碱后引发癫痫发作的N-甲基-D-天冬氨酸的ED50为0.0014μmol（0.001 - 0.0019）。脑电图监测显示海马体和皮质内惊厥活动的模式和演变顺序与单独使用380mg/kg毛果芸香碱时相似。对在黑质网状部注射N-甲基-D-天冬氨酸并随后给予100mg/kg毛果芸香碱且发生癫痫持续状态的大鼠脑进行形态学检查发现，杏仁核、丘脑、嗅觉皮质、黑质、新皮质和海马体均有广泛损伤。双侧向黑质致密部或背侧纹状体微量注射0.002μmol的N-甲基-D-天冬氨酸，不会增强100mg/kg毛果芸香碱所致的癫痫发作。结果表明，大鼠中毛果芸香碱诱导癫痫发作的阈值受黑质网状部内兴奋性氨基酸神经传递的调节。
