ROLE OF EXCITATORY AMINO-ACID AND GABA(B) RECEPTORS IN THE GENERATION OF EPILEPTIFORM ACTIVITY IN DISINHIBITED HIPPOCAMPAL SLICE CULTURES

被引:51
作者
SCANZIANI, M [1 ]
DEBANNE, D [1 ]
MULLER, M [1 ]
GAHWILER, BH [1 ]
THOMPSON, SM [1 ]
机构
[1] UNIV ZURICH, INST BRAIN RES, CH-8029 ZURICH, SWITZERLAND
关键词
D O I
10.1016/0306-4522(94)90405-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Selective excitatory amino acid- and GABA(B)-receptor antagonists were used to examine the role these receptors play in epileptiform burst discharge elicited by blocking GABA, receptor-mediated inhibition in hippocampal slice cultures of the rat. Application of bicuculline caused a single ictal burst followed by interictal bursting. The N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovalerate, reduced the depolarizing envelope underlying interictal discharge, and accentuated the appearance of concomitant slow oscillatory potentials, which occurred synchronously in all CA3 cells. The non-N-methyl-D-aspartate receptor antagonists, 6-nitro-7sulphamoyl-benzo(F)quinoxaline and 6-cyano-7-nitro-quinoxaline-2,3-dione, blocked interictal bursting at high concentrations, and low concentrations of 6-cyano-7-nitro-quinoxaline-2,3-dione selectively eliminated the slow oscillations in an all-or-none manner, leaving the depolarizing envelope. No effects of either metabotropic glutamate receptor antagonists or of dihydropyridine Ca2+ channel agonists or antagonists on evoked interictal discharge were observed. 6-Cyano-7-nitro-quinoxaline-2,3-dione-resistant interictal-like discharge could be obtained in the presence of bicuculline when the external Mg2+ concentration was reduced from 1.5-0.5 mM. The GABA(B) receptor antagonist CGP 35348 prolonged individual evoked interictal bursts, and caused the appearance of spontaneous ictal-like discharges. The implications of these results are discussed with regard to the mechanisms of epileptogenesis and to potential therapeutic intervention.
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页码:823 / 832
页数:10
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