Xu S G, Garant D S, Sperber E F, Moshé S L
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Brain Res Dev Brain Res. 1992 Aug 21;68(2):275-7. doi: 10.1016/0165-3806(92)90070-d.
The substantia nigra gamma-aminobutyric acid (GABA) system is crucial for seizure control. Our previous work indicates that in 16-day-old rat pups, nigral administration of the GABAA receptor agonist muscimol facilitates flurothyl-induced seizures, whereas it suppresses seizures in adult rats. To determine whether the proconvulsant effect of muscimol in rat pups may be mediated by nigral GABAA receptors, in the present study we applied a selective GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Bilateral nigral infusions of THIP (500 or 700 ng) significantly decreased the thresholds for flurothyl seizures in a dose-dependent fashion. Doses of 350 ng or less did not significantly modify the susceptibility to seizures. An anticonvulsant action of THIP could not be detected at any dose. Administration of an effective THIP dose (500 ng) 2 mm dorsal to the SNR had no influence on seizures. These findings suggest that in rat pups the proconvulsant effect of nigral GABAA receptor agonists may be attributed to unique pharmacologic characteristics of GABAA receptors during development.
黑质γ-氨基丁酸（GABA）系统对癫痫控制至关重要。我们之前的研究表明，在16日龄的幼鼠中，向黑质注射GABAA受体激动剂蝇蕈醇会促进氟替尔诱导的癫痫发作，而在成年大鼠中则会抑制癫痫发作。为了确定蝇蕈醇在幼鼠中的促惊厥作用是否可能由黑质GABAA受体介导，在本研究中我们应用了一种选择性GABAA受体激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）。双侧黑质注射THIP（500或700 ng）以剂量依赖的方式显著降低了氟替尔癫痫发作的阈值。350 ng或更低的剂量并未显著改变癫痫易感性。在任何剂量下均未检测到THIP的抗惊厥作用。在黑质网状部（SNR）背侧2 mm处注射有效剂量的THIP（500 ng）对癫痫发作没有影响。这些发现表明，在幼鼠中，黑质GABAA受体激动剂的促惊厥作用可能归因于发育过程中GABAA受体独特的药理学特性。
