Impaired spatial memory in aged rats is associated with alterations in inositol phospholipid metabolism.

WE have investigated changes in inositol phospholipid turnover and membrane arachidonic acid concentration in the dentate gyrus and frontal cortex of animals aged 3-6 months, 14 months or 22 months which were trained in the Morris water maze. Ageing was associated with poorer performances in the behavioural test, characterized by increased variability in retention and acquisition amongst individuals, a decrease in membrane arachidonic acid concentration and increased unstimulated inositol phospholipid metabolism in synaptosomes prepared from frontal cortex and dentate gyrus. Arachidonic acid stimulated inositol phospholipid metabolism in synaptosomes, but in the older groups, stimulation was associated with good performance in the Morris water maze. In slices prepared from frontal cortex, responsiveness of inositol phospholipid metabolism to glutamate was also age- and performance-dependent. The findings highlight a correlation between age, inositol phospholipid metabolism and performance in the Morris water maze.