Garant D S, Xu S G, Sperber E F, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Epilepsia. 1995 Oct;36(10):960-5. doi: 10.1111/j.1528-1157.1995.tb00953.x.
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 GABAA receptor agonist muscimol results in a biphasic dose-response curve in adults: Intermediate doses are anticonvulsant, but high doses have proconvulsant effects. Another GABAA 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 GABAA 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 GABAA-sensitive neuronal circuits in the SNR.
黑质网状部（SNR）中的γ-氨基丁酸能传递在实验性癫痫发作的控制中起着重要作用。在氟替尔癫痫模型中，向SNR微量注射选择性γ-氨基丁酸A受体激动剂蝇蕈醇在成年动物中产生双相剂量反应曲线：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γ-氨基丁酸A受体激动剂，THIP（4,5,6,7-四氢异恶唑并-[5,4-c]吡啶-3-醇），在较低剂量时也产生抗惊厥作用，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，且所需剂量低于成年动物。这些数据表明，未成熟的SNR对γ-氨基丁酸A受体激动剂的促惊厥作用比成年动物的SNR更敏感得多。我们推测，黑质γ-氨基丁酸能反应中与年龄相关的差异可能是由于SNR中γ-氨基丁酸A受体敏感神经元回路的个体发育变化所致。
