HUMAN NERVE GROWTH-FACTOR IMPROVES SPATIAL MEMORY IN AGED BUT NOT IN YOUNG-RATS

The behavioral effects of human nerve growth factor (NGF) were assesse d in Fischer-344 rats of two ages: 4 months old (4MO) and 23 months ol d (23MO). Recent memory was tested in delayed alternation (T maze), re ference memory in a place discrimination (water maze), and sensorimoto r skills in a battery of sensorimotor tasks. Each rat was preoperative ly trained in each task, given either a central procedure (CON), or co ntinuous infusion of human NGF via an osmotic minipump, and retested a gain 3 weeks later. Two doses of NGF were delivered: 40 mu g and 160 m u g (total amount infused over a period of 4 weeks). In 23MO-NGF rats, both doses improved performance in the recent memory task, and in som e measures of the place learning task, but had no effect on sensorimot or skills. In 4MO-NGF rats, the low dose impaired performance in the r ecent memory task, but not in the place discrimination or in the senso rimotor tasks. These data indicate that human NGF can reverse age-rela ted cognitive impairments in old rats. However, the present study also raises the issue of potential detrimental effects that NGF may exert in young normal subjects.