Effects of NMDA receptor antagonists on passive avoidance learning and retrieval in rats and mice

The effects of NMDA antagonists on passive avoidance learning, shock sensitivity and locomotor activity were examined. Pre-training administration of the antagonists 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) in mice and rats resulted in impaired performance in a retention test 24 h later. No such impairment resulted from immediate post-training administration of either compound in either species. In addition neither compound, given only before the retention test, reduced the retention latencies of mice. In rats CPP was similarly ineffective whereas MK-801 reduced retention latencies, but only at a dose which significantly elevated locomotor activity at the time of the retention test. As assessed by vocalization threshold in mice and by the proportion of animals vocalizing in response to the passive avoidance training shock, neither compound produced analgesia. The vocalization threshold was, in fact, slightly reduced by both compounds. MK-801, but not CPP, stimulated locomotor activity in mice. These results indicate that in the passive avoidance task activation of NMDA receptors is involved in memory formation, but is not critical for the maintenance of memory or its retrieval.