丙戊酸可抑制大鼠杏仁核切片中由NMDA受体介导的突触反应。

Valproic acid suppresses the synaptic response mediated by the NMDA receptors in rat amygdalar slices.

作者信息

Gean P W, Huang C C, Hung C R, Tsai J J

机构信息

Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, R.O.C.

出版信息

Brain Res Bull. 1994;33(3):333-6. doi: 10.1016/0361-9230(94)90202-x.

DOI:10.1016/0361-9230(94)90202-x

PMID:7904890

Abstract

The mechanism of action of the anticonvulsant drug valproic acid (VPA) was studied in rat amygdaloid slices using intracellular recording techniques. In the presence of bicuculline (20 microM), stimulation of the endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP) followed by a paroxysmal depolarizing shift (PDS). Superfusion of VPA (2 mM) reversibly suppressed the PDS. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was isolated pharmacologically by application of a solution containing nonNMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and gamma-aminobutyric acid receptor antagonist bicuculline (20 microM). VPA (0.2-10 mM) reversibly reduced the amplitude of the EPSPNMDA in a dose-dependent manner. Higher concentration of VPA (10 mM), in addition, suppressed the normal synaptic transmission. These results suggest that VPA's anticonvulsant effect is due, at least in part, to its blocking action on the EPSPNMDA.

摘要

使用细胞内记录技术在大鼠杏仁核切片中研究了抗惊厥药物丙戊酸（VPA）的作用机制。在荷包牡丹碱（20微摩尔）存在的情况下，刺激梨状体内核诱发兴奋性突触后电位（EPSP），随后是阵发性去极化偏移（PDS）。VPA（2毫摩尔）的灌流可逆地抑制了PDS。通过应用含有非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）和γ-氨基丁酸受体拮抗剂荷包牡丹碱（20微摩尔）的溶液，药理学上分离了由N-甲基-D-天冬氨酸（NMDA）受体介导的突触反应（EPSPNMDA）。VPA（0.2 - 10毫摩尔）以剂量依赖性方式可逆地降低EPSPNMDA的幅度。此外，较高浓度的VPA（10毫摩尔）抑制正常的突触传递。这些结果表明，VPA的抗惊厥作用至少部分归因于其对EPSPNMDA的阻断作用。