Memory deficits induced byγ-l-glutamyl-l-aspartate andd-2-amino-5-phosphonovalerate in a Y-maze avoidance task: relationship to NMDA receptor antagonism
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Abstract
Post-training administration (ICV) ofγ-l-glutamyl-l-aspartate (γ-lGLA) ord-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 ofγ-lGLA andd-AP5 to decrease retention, with maximum effects occurring at doses of 2–20 nmol/mouse forγ-lGLA and 0.02 nmol/mouse ford-AP5.γ-lGLA andd-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 byγ-lGLA andd-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 nmolγ-lGLA and by 0.3 nmold-AP5. Taken together, these results are consistent with previous studies suggesting that the behavioral effects ofγ-lGLA might be related to its NMDA receptor antagonist properties. The selectivity of the memory deficits induced byγ-lGLA andd-AP5 is in agreement with recent reports suggesting a role for NMDA receptors in the mechanisms underlying posttraining organization of memory traces.
Key words
NMDA receptor Peptide Memory Ataxia Seizure MousePreview
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