THE EFFECTS OF INTRAHIPPOCAMPAL BDNF AND NGF ON SPATIAL-LEARNING IN AGED LONG-EVANS RATS

Spatial learning rate was compared in cognitively impaired aged rats i nfused with either brain-derived neurotrophic factor (BDNF) or nerve g rowth factor (NGF). BDNF or NGF was infused into the dorsal hippocampu s/third ventricle while animals were being trained on the Morris water maze. Training continued until all rats met a spatial learning criter ion. Seven weeks later, they were tested for retention of the task, an d sacrificed for assessment of hippocampal high-affinity choline uptak e (HACU) or hypothalamic biogenic amine levels. NGF, but not BDNF, imp roved spatial learning rate in aged rats and increased hippocampal cho line uptake weeks after withdrawal of NGF. Although BDNF did not impro ve spatial learning, it did induce a partial, long-term normalization of the elevated hypothalamic 5-HT levels observed in our aged rats. Th ese data suggest that (1) intrahippocampal/intraventricular infusion o f NGF can improve the learning rate of aged, spatial learning-impaired rats, and that this improvement in acquisition could be associated wi th increased hippocampal cholinergic activity, and (2) that the BDNF-i nduced normalization of hypothalamic 5-HT levels in aged rats was not sufficient to improve learning rate in aged, spatial learning-impaired rats.