A GLYCINE ANTAGONIST 7-CHLOROKYNURENIC ACID ATTENUATES ISCHEMIA-INDUCED LEARNING-DEFICITS

被引：29

作者：

WOOD, ER ^{[1
]}

BUSSEY, TJ ^{[1
]}

PHILLIPS, AG ^{[1
]}

机构：

[1] UNIV BRITISH COLUMBIA, DEPT PSYCHOL, 2163 W MALL, VANCOUVER V6T 1Z4, BC, CANADA

来源：

NEUROREPORT | 1993年 / 4卷 / 02期

关键词：

EXCITOTOXICITY; ISCHEMIA; GLYCINE; GLUTAMATE; HIPPOCAMPUS; LEARNING; MEMORY; NMDA RECEPTOR;

D O I：

10.1097/00001756-199302000-00009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

TRANSIENT global ischemia can result in permanent neuronal damage and impairments in learning and memory. We investigated the therapeutic potential of 7-Chlorokynurenic acid, a potent antagonist at the glycine-modulatory site on the NMDA receptor, in terms of both neuroprotection and behavioral outcome in rats following transient forebrain ischemia. Intraventricular administration of the drug immediately before ischemia significantly attenuated ischemia-induced CA1 pyramidal cell loss. Morevoer, ischemic rats treated with 7-Chlorokynurenic acid showed unimpaired acquisition of a delayed nonmatching to sample task 8 weeks following surgery, whereas saline-treated ischemic rats were significantly impaired. These data provide preliminary evidence that the glycine site may be an appropriate target for therapeutic agents in ischemia.

引用

页码：151 / 154

页数：4

共 18 条

[1] MNEMONIC AND NEUROPATHOLOGICAL EFFECTS OF OCCLUDING THE POSTERIOR CEREBRAL-ARTERY IN MACACA-MULATTA [J].

BACHEVALIER, J ;

MISHKIN, M .

NEUROPSYCHOLOGIA, 1989, 27 (01) :83-105

[2] THE N-METHYL-D-ASPARTATE ANTAGONISTS CGS-19755 AND CPP REDUCE ISCHEMIC BRAIN-DAMAGE IN GERBILS [J].

BOAST, CA ;

GERHARDT, SC ;

PASTOR, G ;

LEHMANN, J ;

ETIENNE, PE ;

LIEBMAN, JM .

BRAIN RESEARCH, 1988, 442 (02) :345-348

[3]

DAVIS HP, 1990, BIOL MEMORY S MED HO, V23, P477

[4]

Dingledine R., 1990, EXCITATORY AMINO ACI, P17, DOI 10. 1007/978-1-4684-5769-8_3

[5]

GILL R, 1987, BRIT J PHARMACOL, V91, P311

[6] NEUROTOXIN-RELATED RESEARCH - FROM THE LABORATORY TO THE CLINIC [J].

IVERSEN, L ;

FOSTER, AC ;

HILL, RG ;

IVERSEN, SD ;

KEMP, JA ;

LEESON, PD ;

RUPNIAK, NMJ ;

SAYWELL, K ;

TRICKLEBANK, MD ;

WILLIAMS, BJ .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1992, 648 :207-218

[7] 7-CHLOROKYNURENIC ACID IS A SELECTIVE ANTAGONIST AT THE GLYCINE MODULATORY SITE OF THE N-METHYL-D-ASPARTATE RECEPTOR COMPLEX [J].

KEMP, JA ;

FOSTER, AC ;

LEESON, PD ;

PRIESTLEY, T ;

TRIDGETT, R ;

IVERSEN, LL ;

WOODRUFF, GN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (17) :6547-6550

[8] REQUIREMENT FOR GLYCINE IN ACTIVATION OF NMDA-RECEPTORS EXPRESSED IN XENOPUS OOCYTES [J].

KLECKNER, NW ;

DINGLEDINE, R .

SCIENCE, 1988, 241 (4867) :835-837

[9] GLUTAMATE AND GLYCINE CO-ACTIVATE WHILE POLYAMINES MERELY MODULATE THE NMDA RECEPTOR COMPLEX [J].

LEHMANN, J ;

COLPAERT, F ;

CANTON, H .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 1991, 15 (02) :183-190

[10] GLYCINE DECREASES DESENSITIZATION OF N-METHYL-D-ASPARTATE (NMDA) RECEPTORS EXPRESSED IN XENOPUS-OOCYTES AND IS REQUIRED FOR NMDA RESPONSES [J].

LERMA, J ;

ZUKIN, RS ;

BENNETT, MVL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (06) :2354-2358

← 1 2 →