Chronic intracerebroventricular NGF administration improves working memory in young adult memory deficient rats

Although the beneficial effects of nerve growth factor (NGF) in age-related memory deficits are well documented, the therapeutic role of this neurotrophin in memory deficits occurring in young Subjects remains unclear. In the present study, the effect of chronic NGF administration on spatial working memory was investigated in young adult memory deficient Wistar rats. Memory deficient rats were selected on the basis of their preoperative performance in delayed matching-to-position task (DMTP) carried out in the eight-arm radial maze. The delay between sample and test choices was prolonged stepwise from 10 s, to 1, 5, and eventually 15 min. Rats that performance at the longest 15-min delay was at least 3 S.E.M. above the group mean were classified as "poor learners". They were randomly assigned to either Control or NGF group, and treated with either vehicle solution (artificial cerebrospinal fluid) or NGF at the total dose of 40 mu g/rat. Intracerebroventricular (icv) drug infusion was made continuously over 28 days at the rate of 0.25 mu l/h using Alzet 2004 osmotic mini-pump. The postoperative training included the same stages as the preoperative one. No significant between-group difference in the postoperative performance was noted at the shortest delay of 10 s that could be bridged by the immediate memory. Conversely, at all three longer delays, postoperative performance in the NGF group was significantly better compared to control rats. The present study thus shows that NGF may have beneficial effects in memory-deficient young adults. (c) 2005 Elsevier Ireland Ltd. All rights reserved.