MK-801 improves retention in aged rats: Implications for altered neural plasticity in age-related memory deficits

Alterations in N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic pla sticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine wheth er NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22 -24 months) and adult (3-6 months) male Fischer 344 rats received 18 traini ng trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial wa s administered to assess the acquisition of spatial bias, which was determi ned by the percent of time spent in the goal quadrant and the number of pla tform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10,11-dihydro-5-methyl-5H-dibenzo(a,b)cycloheptene-5,10 imi ne (MK-801, 0.05 mg/kg, ip), or a vehicle injection of equal volume. Approx imately 24 h later, rats were administered a second free-swim probe trial t o assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the age d rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, sugg esting that NMDAR activity may be involved in rapid forgetting during aging . Because blockade of NMDARs also may impair new learning, which may, in tu rn, protect previously stored information from retroactive interference, ra ts in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine di d not enhance retention in the aged group, consistent with the hypothesis t hat MK-801 influenced memory in aged rats through its actions on NMDAR-depe ndent synaptic plasticity. (C) 1999 academic Press.