gamma-L-glutamyl-L-aspartate induces specific deficits in long-term memory and inhibits [3H]glutamate binding on hippocampal membranes.
gamma-L-Glutamyl-L-aspartic acid (gamma-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. gamma-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 gamma-LGLA was specific to the peptide. gamma-LGLA impaired learning acquisition in a time-dependent manner when administered from 3 min to 24 h post-training, but had no effect when administered 3 days following acquisition. gamma-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. gamma-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 gamma-LGLA on excitatory amino acid systems which may be responsible for its effects on learning retention.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004644:Emotions; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors
D000596:Amino Acids; D004151:Dipeptides; D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C021030:gamma-glutamylaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid