GABAB receptor activation exacerbates spontaneous spike-and-wave discharges in DBA/2J mice
GABAB receptor activation exacerbates spontaneous spike-and-wave discharges in DBA/2J mice
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DOI：
10.1016/j.seizure.2010.02.007
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发表时间：
2010-05-01
影响因子：
3
通讯作者：
Marrosu, Francesco
中科院分区：
文献类型：
--
作者：
Bortolato, Marco;Frau, Roberto;Marrosu, Francesco
大量证据表明，刺激γ-氨基丁酸(GABA)(B)受体可增加失神癫痫(AE)的脑电标志物--棘波放电(SWDS)的发生。最近的发现表明，体内GABA(B)激活的结果取决于激动剂的化学特性。特别是，内源性配体羟丁酸酯(GHB)及其前体伽马丁内酯(GBL)的作用与典型的GABA(B)激动剂巴氯芬不同。鉴于这些前提，本研究旨在描述巴氯芬(0.5-10 mg/kg，i.p.)的作用。GBL(5-100 mg/kg，i.p.)巴氯芬和银杏叶提取物均可剂量依赖性地增加DBA/2J小鼠的自发游泳次数，但高剂量(100 mg/kg)的银杏叶提取物可使DBA/2J小鼠自发游泳次数增加。减少了这些现象的发生，增加了孤立尖峰的数量。有趣的是，这两种化合物与它们的赋形剂处理的对照组相比，都引起了剂量依赖性的运动活动减少。GABA(B)选择性拮抗剂SCHS0911(50 mg/kg，ip)能逆转巴氯芬和GBL引起的SWD的发生和运动改变，但不能对这两种范式产生内源性效应。这些结果表明，GABA(B)受体信号通路可能在DBA/2J小鼠SWDS中发挥不同的作用。(C)2010年英国癫痫协会。爱思唯尔有限公司出版。保留所有权利。
Rich evidence has highlighted that stimulation of gamma-amino-butyric acid (GABA)(B) receptors increases the occurrence of spike-and-wave discharges (SWDs), the electroencephalographic (EEG) landmark of absence epilepsy (AE). Recent findings suggest that the outcomes of GABA(B) activation in vivo are contingent on the chemical characteristics of the agonist. In particular, the endogenous ligand hydroxybutyrate (GHB) and its precursor gamma-butyro-lactone (GBL) have been shown to elicit different effects than the prototypical GABA(B) agonist baclofen. In view of these premises, the present study was aimed at the characterization of the effects of baclofen (0.5-10 mg/kg, i.p.) and GBL (5-100 mg/kg, i.p.) on the spontaneous SWDs and locomotor activity of DBA/2J mice.While both baclofen and GBL dose-dependently increased SWDs episodes, high doses of the latter (100 mg/kg, i.p.) reduced the occurrence of these phenomena and increased the number of isolated spikes. Interestingly, both compounds elicited a dose-dependent reduction of locomotor activity, in comparison with their vehicle-treated controls. The GABA(B) selective antagonist, SCHS0911 (50 mg/kg, i.p.), reversed the changes in SWD occurrence and locomotion induced by baclofen and GBL, but failed to elicit intrinsic effects on either paradigm. These results indicate that GABA(B) receptor signaling might exert differential effects on SWDs in DBA/2J mice. (C) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.