Memory deficits induced by gamma-L-glutamyl-L-aspartate and D-2-amino-6-phosphonovalerate in a Y-maze avoidance task: relationship to NMDA receptor antagonism.
Post-training administration (ICV) of gamma-L-glutamyl-L-aspartate (gamma-LGLA) or D-2-amino-5-phosphonovalerate (D-AP5), a competitive NMDA antagonist, decreased retention of the temporal component but not the spatial discrimination component of a Y-maze active avoidance task. Inverted U-shaped dose-response curves were obtained for the ability of gamma-LGLA and D-AP5 to decrease retention, with maximum effects occurring at doses of 2-20 nmol/mouse for gamma-LGLA and 0.02 nmol/mouse for D-AP5. gamma-LGLA and D-AP5 impaired the traction reflex only at doses (80 and 2 nmol/mouse, respectively) higher than those producing retention deficits. Convulsions induced by ICV administration of 1 nmol NMDA were antagonized by gamma-LGLA and D-AP5 with ED50 values of 46 (32-66) and 0.2 (0.16-0.25) nmol/mouse, respectively. The dose-effect curve of NMDA for producing convulsions was shifted to the right in a parallel manner and to the same extent by 80 nmol gamma-LGLA and by 0.3 nmol D-AP5. Taken together, these results are consistent with previous studies suggesting that the behavioral effects of gamma-LGLA might be related to its NMDA receptor antagonist properties. The selectivity of the memory deficits induced by gamma-LGLA and D-AP5 is in agreement with recent reports suggesting a role for NMDA receptors in the mechanisms underlying posttraining organization of memory traces.
Laboratoire de Psychophysiologie, Université Louis Pasteur, URA 1295 CNRS, Strasbourg, France.
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Mathis
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de Barry
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Ungerer
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects; D013647:Task Performance and Analysis
D000927:Anticonvulsants; D004151:Dipeptides; D016194:Receptors, N-Methyl-D-Aspartate; C021030:gamma-glutamylaspartic acid; D015763:2-Amino-5-phosphonovalerate