THE EFFECTS OF NERVE GROWTH-FACTOR ON SPATIAL RECENT MEMORY IN AGED RATS PERSIST AFTER DISCONTINUATION OF TREATMENT

Nerve growth factor (NGF) infusion significantly reduces spatial recen t memory deficits in aged rats, an effect that has great relevance to the treatment of memory impairments characteristic of patients with Al zheimer's disease. The present study was designed to examine whether t his NGF-induced improvement in spatial recent memory persists after th e discontinuation of NGF treatment, an issue of crucial importance for the potential clinical use of this compound. Spatial recent memory wa s tested in a Morris water maze delayed nonmatch-to-position task. In addition to memory, sensorimotor skills were also examined. Four- and 22-month-old rats were tested preoperatively, infused intraventricular ly with recombinant human NGF or vehicle, and tested both during the 4 week infusion period and during the 4 weeks after discontinuation of the infusion. NGF significantly improved spatial recent memory in 23-m onth-old rats only, during the 4th week of infusion and for up to 4 we eks after discontinuation of the infusion. Although NGF did not affect overall sensorimotor skills during infusion in either age group, sens orimotor skills were significantly improved both 2 and 4 weeks after d iscontinuation of infusion in 22-month-old rats. These findings demons trate that the beneficial effects of NGF on spatial recent memory can persist for up to 1 month after discontinuation of infusion and sugges t that NGF can be used intermittently for the treatment of age-associa ted memory dysfunction and Alzheimer's disease.