Burade V S, Jain M R, Khan F A, Saha S G, Subhedar N
Department of Pharmaceutical Sciences, Nagpur University Campus, India.
Neuroreport. 1996 Dec 20;8(1):139-41. doi: 10.1097/00001756-199612200-00028.
Recent reports have confirmed the involvement of neurosteroids in a number of neurophysiological processes, including sleep, and that these compounds interact with the gamma-aminobutyric acid receptor A complex. As many of the behavioural effects of pentobarbital are as a result of the activity at this complex, we investigated the role of corticosteroid-like neurosteroids in regulation of sleep, using metyrapone as a tool. Metyrapone, a blocker of the enzyme 11 beta-hydroxylase, which is essential for the biosynthesis of corticosteroids, when administered intracerebroventricularly (i.c.v.) at low doses (50-5000 ng) caused a dose-dependent reduction in sleep time induced by pentobarbital. This effect was, however, antagonized by concomitant administration of anti-corticotropin-releasing factor antisera. The present study reveals for the first time that corticosteroid-like neurosteroids might be involved in the regulation of CNS excitability.
近期报告已证实神经甾体参与了包括睡眠在内的多种神经生理过程，且这些化合物可与γ-氨基丁酸A型受体复合物相互作用。由于戊巴比妥的许多行为效应是由该复合物的活性所致，我们使用甲吡酮作为工具，研究了皮质类固醇样神经甾体在睡眠调节中的作用。甲吡酮是一种11β-羟化酶的阻滞剂，该酶对皮质类固醇的生物合成至关重要，当以低剂量（50 - 5000纳克）脑室内给药时，可导致戊巴比妥诱导的睡眠时间呈剂量依赖性减少。然而，同时给予抗促肾上腺皮质激素释放因子抗血清可拮抗这种效应。本研究首次揭示皮质类固醇样神经甾体可能参与中枢神经系统兴奋性的调节。
