γ- l-Glutamyl- l-aspartate induces specific deficits in long-term memory and inhibits [ 3H]glutamate binding on hippocampal membranes

Abstract

γ- l-Glutamyl- l-aspartic acid (γ-LGLA) has been isolated from Datura stramonium; its structure has been determined and it was then synthesized. In male Swiss mice intraperitoneal administration of the natural peptide (125 nmol/kg) or of the synthetic peptide (25–2500 nmol/kg) 24 h after acquisition of a Y-maze avoidance task induced a dose-dependent deficit in retention performance 48 h later. γ-LGLA had no effect on locomotor activity or emotional reactivity at the doses used. Separate or simultaneous administration of aspartate or glutamate (each at 250 nmol/kg) had no effect on learning retention, indicating that deficit induced by γ-LGLA was specific to the peptide. γ-LGLA impaired learning acquisition in a time-dependent manner when administered juom 3 min to 24 h post-training, but had no effect when administered 3 days following acquisition. γ-LGLA administered just after the training session did not affect retention performance during the first 3 h, but suppressed the retention improvement observed in control animals from 6 to 24 h after acquisition; this deficit was still evident 7 days after the treatment. γ-LGLA partially inhibited l-[ 3H]glutamate binding on crude hippocampal or striatal membrane preparations; this inhibition was not observed on cerebellar membrane preparations. These results suggest a specific action of γ-LGLA on excitatory amino acid systems which may be responsible for its effects on learning retention.