N-methyl-D-aspartate receptor density and membrane fluidity as possible determinants of the decline of passive avoidance performance in aging.

The effect of aging on three different parameters possibly relevant for cognition was investigated in female Naval Medical Research Institute mice: a) N-methyl-D-aspartate (NMDA) receptor density, as determined by the specific binding of [3H]MK-801 to forebrain membranes, decreased by 22% in aged (23 mo) and by 19% in middle-aged (12 mo) animals compared with young (3 mo) animals. b) In a passive avoidance acquisition task, the 24-h latency decreased significantly with age; the middle-aged mice also tended to show impairment in this task. c) The fluidity of the forebrain membranes also decreased significantly with age. Again, there was a significant reduction in the middle-aged group. A comparison of these parameters revealed significant correlations between NMDA receptor density and 24-h latency (r = 0.52, p < 0.003) over all three age groups, as well as significant correlations between membrane fluidity and either NMDA receptor density or 24-h latency. These findings do not prove a causal relationship, but are compatible with the hypothesis that changes of membrane fluidity, by decreasing the number of NMDA receptors, affect passive avoidance performance.