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Volume 17, Number 7, Issue of April 1, 1997 pp. 2543-2550
Copyright ©1997 Society for Neuroscience

The Effects of Nerve Growth Factor on Spatial Recent Memory in Aged Rats Persist after Discontinuation of Treatment

Received Sept. 27, 1996; revised Dec. 5, 1996; accepted Dec. 11, 1996.

Karyn M. Frick¹, Donald L. Price², Vassilis E. Koliatsos², and Alicja L. Markowska¹

¹ Department of Psychology, The Johns Hopkins University, Baltimore, Maryland 21218, and ² Departments of Pathology, Neurology, and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Nerve growth factor (NGF) infusion significantly reduces spatial recent memory deficits in aged rats, an effect that has great relevance to the treatment of memory impairments characteristic of patients with Alzheimer's disease. The present study was designed to examine whether this NGF-induced improvement in spatial recent memory persists after the discontinuation of NGF treatment, an issue of crucial importance for the potential clinical use of this compound. Spatial recent memory was 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 intraventricularly 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 22-month-old rats only, during the 4th week of infusion and for up to 4 weeks after discontinuation of the infusion. Although NGF did not affect overall sensorimotor skills during infusion in either age group, sensorimotor skills were significantly improved both 2 and 4 weeks after discontinuation of infusion in 22-month-old rats. These findings demonstrate that the beneficial effects of NGF on spatial recent memory can persist for up to 1 month after discontinuation of infusion and suggest that NGF can be used intermittently for the treatment of age-associated memory dysfunction and Alzheimer's disease.

Key words: neurotrophins; aging; water maze; delayed nonmatch-to-position; working memory; body weight

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