神经活性甾体加重γ-羟基丁酸诱导的大鼠失神发作。

Neuroactive steroids exacerbate gamma-hydroxybutyric acid-induced absence seizures in rats.

作者信息

Banerjee P K, Snead O C

机构信息

Hospital for Sick Children, Department of Pediatrics, University of Toronto, Ontario, Canada.

出版信息

Eur J Pharmacol. 1998 Oct 16;359(1):41-8. doi: 10.1016/s0014-2999(98)00629-3.

DOI:10.1016/s0014-2999(98)00629-3

PMID:9831291

Abstract

Certain naturally-occurring steroid metabolites and their synthetic analogs (neuroactive steroids) allosterically enhance GABA(A) receptor function and possess potent anticonvulsant properties. In the present study, the effect of two synthetic neuroactive steroids, alphaxalone (5alpha-pregnane 3alpha-ol-11, 20-dione) and tetrahydrodeoxycorticosterone was studied in a rat model of generalized absence seizures induced by gamma-hydroxybutyric acid. Both steroids dose-dependently exacerbated gamma-hydroxybutyric acid-induced absence seizures upon systemic administration and after focal administration into thalamic ventrobasal nucleus. However, alphaxalone and tetrahydrodeoxycorticosterone failed to potentiate gamma-hydroxybutyric acid-induced absence seizures when injected into thalamic reticular nucleus. In all the doses of steroids tested in thalamic reticular nucleus, the duration of gamma-hydroxybutyric acid-seizures was neither prolonged nor shortened. This nonresponsiveness of thalamic reticular nucleus to neuroactive steroids in modulating absence seizures may have arisen due to the molecular heterogeneity of GABA(A) receptor subunits within the thalamus.

摘要

某些天然存在的甾体代谢产物及其合成类似物（神经活性甾体）可别构增强GABA(A)受体功能，并具有强大的抗惊厥特性。在本研究中，研究了两种合成神经活性甾体，α-羟孕酮（5α-孕烷-3α-醇-11,20-二酮）和四氢脱氧皮质酮，在γ-羟基丁酸诱导的大鼠全身性失神发作模型中的作用。全身给药以及向丘脑腹侧基底核局部给药后，两种甾体均剂量依赖性地加重γ-羟基丁酸诱导的失神发作。然而，当注入丘脑网状核时，α-羟孕酮和四氢脱氧皮质酮未能增强γ-羟基丁酸诱导的失神发作。在丘脑网状核中测试的所有甾体剂量下，γ-羟基丁酸发作的持续时间既未延长也未缩短。丘脑网状核对神经活性甾体在调节失神发作方面的这种无反应性可能是由于丘脑内GABA(A)受体亚基的分子异质性所致。