Guido Lenz

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 nerve growth factor (NGF) infusion has a beneficial effect on cognitive performance 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 hippocampus on inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in time and space, of NGF infusion into CA1 on the activity of mitogen‐activated protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0u2003ng diluted in 0.5u2003μL of saline per side) at 0, 120 or 360u2003min after IA training in rats. Retention testing was carried out 24u2003h after training. The injection of 5.0 and 0.5, but not 0.05, ng per side of NGF at 0 and 120u2003min after IA training enhanced IA retention. The highest dose used was ineffective when injected 360u2003min after training. The infusion of 0.5u2003μL of NGF (5.0u2003ng) induced a significant enhancement of MAPK activity in hippocampal microslices; this enhancement was restricted to a volume with 0.8u2003mm radius at 30u2003min after injection. The MAPK activation was still seen 180u2003min after NGF infusion, although this value showed only a tendency. In conclusion, localized infusion of NGF into the CA1 region enhanced MAPK activity, restricted in time and space, and enhanced IA retention in a time‐ and dose‐dependent manner.