Strain-dependent effects of gamma-L-glutamyl-L-aspartate, a NMDA antagonist, on retention of a Y-maze avoidance learning task in mice.

The NMDA receptor antagonist, gamma-L-glutamyl-L-aspartate (gamma-LGLA), suppressed spontaneous improvement in posttraining performance in Swiss mice during the hours following acquisition of a Y-maze avoidance learning task. Since variability in posttraining performance is at least partially due to genetic factors, we compared the effects of gamma-LGLA on retention of Y-maze learning in C57BL/6J, DBA/2J and BALB/c mice. Mice had to leave the start alley of the maze within the first 5 s (temporal component) and to choose the left alley (spatial component). C57BL mice significantly improved their performance from 1 h to 24 h posttraining, whereas DBA/2J and BALB/c mice did not. However, only retention of the temporal component improved over time in C57BL. gamma-LGLA administered immediately posttraining (0.025-25 mumol/kg, i.p.) dose-dependently impaired retention of the temporal component in C57BL mice 48 h later, but had no significant effect on retention of the spatial component. gamma-LGLA administered 24 h posttraining induced a similar but weaker deficit. In contrast, gamma-LGLA did not significantly affect retention of DBA/2J and BALB/c mice, regardless of the component analyzed or the time of administration. It had no effect on locomotor activity or emotional reactivity of animals of any strain. These results support the hypothesis of a specific action of gamma-LGLA on mechanisms involved in the treatment of information during the hours following acquisition, and suggest that NMDA receptors are involved in this action.