The NMDA receptor antagonists, CPP and gamma-L-glutamyl-L-aspartate, selectively block post-training improvement of performance in a Y-maze avoidance learning task.

Behavioral effects of CCP and gamma-L-glutamyl-L-aspartate (gamma-LGLA) were studied in a Y-maze avoidance learning task. Male Swiss mice had to leave the start alley of the maze within the first 5 s of a trial (temporal component) and to choose the left alley (spatial component) to avoid footshocks; they were trained to a criterion of 7 correct out of 8 consecutive trials. CPP and gamma-LGLA when administered immediately following the learning session (0.025-200 mumol/kg, i.p.) significantly impaired retention 48 h later at doses of 0.025-0.25 and 0.25-25 mumol/kg, respectively, but had no significant effect at higher doses. CPP, when administered 30 min before the learning session (0.025-25 mumol/kg) did not affect learning acquisition at any dose, whereas it significantly impaired retention 48 h later but only at the doses of 0.025-0.25 mumol/kg. CPP and gamma-LGLA did not erase all memory traces; posttraining performances on the temporal component, which significantly improved in control animals during the hours following acquisition, were much more affected by CPP and gamma-LGLA than posttraining performances on the spatial component which did not improve over time in controls. Moreover, CPP (0.025-25 mumol/kg) had no effect on spatial recognition memory in an alternation task in which no spontaneous improvement of posttraining performance was observed in controls. These results strongly suggest that CPP and gamma-LGLA interfere with mechanisms underlying posttraining organization of memory traces and that NMDA receptors are involved in this action.