AGE-RELATED DIFFERENCES IN THE EFFECTS OF GABA(A) AGONISTS MICROINJECTED INTO RAT SUBSTANTIA-NIGRA - PROCONVULSANT AND ANTICONVULSANT ACTIONS
AGE-RELATED DIFFERENCES IN THE EFFECTS OF GABA(A) AGONISTS MICROINJECTED INTO RAT SUBSTANTIA-NIGRA - PROCONVULSANT AND ANTICONVULSANT ACTIONS
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DOI：
10.1111/j.1528-1157.1995.tb00953.x
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发表时间：
1995-10-01
期刊：
影响因子：
5.6
通讯作者：
MOSHE, SL
中科院分区：
文献类型：
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作者：
GARANT, DS;XU, SG;MOSHE, SL
黑质网状部（SNR）的GABA能传递在实验性癫痫发作的控制中具有重要作用。在Flurothyl癫痫发作模型中，SNR微量注射选择性GABA（A）受体激动剂蝇蕈醇导致成人出现双相剂量反应曲线：中等剂量具有抗惊厥作用，但高剂量具有促惊厥作用。另一种GABA（A）激动剂THIP（4，5，6，7-tetrahydroisoxazolo-[5，4-c]pyridin-3-ol）在较低剂量下也产生抗惊厥作用，而较高剂量往往产生促惊厥作用。在16日龄的幼鼠中，蝇蕈醇没有抗惊厥作用，只有促惊厥作用，且剂量低于成年大鼠。这些数据表明，未成熟的SNR比成人的SNR对GABA（A）受体激动剂的促惊厥作用更敏感。我们推测，黑质GABA能反应的年龄相关差异可能是由于SNR中GABA（A）敏感神经元回路的个体发生性变化。
GABAergic transmission in the substantia nigra pars reticulata (SNR) has an important role in the control of experimental seizures. In the flurothyl seizure model, SNR microinjection of the selective GABA(A) receptor agonist muscimol results in a biphasic dose-response curve in adults: Intermediate doses are anticonvulsant, but high doses have proconvulsant effects. Another GABA(A) agonist, THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol), also produces anticonvulsant effects at lower doses, whereas higher doses tend to produce a proconvulsant effect. In 16-day-old rat pups, no anticonvulsant but only proconvulsant effects of muscimol occur, and at lower doses than in adults. These data suggest that the immature SNR is significantly more sensitive to the proconvulsant effects of GABA(A) receptor agonists than is the SNR of adults. We hypothesize that the age-related differences in nigral GABAergic response may be due to ontogenic changes in GABA(A)-sensitive neuronal circuits in the SNR.