Time-dependent enhancement of inhibitory avoidance retention and MAPK activation by post-training infusion of nerve growth factor into CA1 region of hippocampus of adult rats

Several studies have demonstrated that chronic intracerebroventricular nerv e growth factor (NGF) infusion has a beneficial effect on cognitive perform ance of lesioned as well as old and developing animals. Here we investigate : (i) the effect of post-training infusion of NGF into the CA1 region of hi ppocampus on inhibitory avoidance (IA) retention in rats; (ii) the extensio n of the effect, in time and space, of NGF infusion into CA1 on the activit y of mitogen-activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NG F was bilaterally injected into the CA1 regions of the dorsal hippocampus ( 0.05, 0.5 or 5.0 ng diluted in 0.5 mu L of saline per side) at 0, 120 or 36 0 min after IA training in rats. Retention testing was carried out 24 h aft er training, The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360 min after training. The infusion of 0.5 mu L of NGF (5.0 ng) induced a significant enhancement of MARK activit y in hippocampal microslices; this enhancement was restricted to a volume w ith 0.8 mm radius at 30 min after injection. The MARK activation was still seen 180 min after NGF infusion, although this value showed only a tendency . In conclusion, localized infusion of NGF into the CA1 region enhanced MAP K activity, restricted in time and space, and enhanced IA retention in a ti me- and dose-dependent manner.