Effect of delayed treatment with nerve growth factor on choline acetyltransferase activity in the cortex of rats with lesions of the nucleus basalis magnocellularis: dose requirements.

Rats received bilateral ibotenic acid-lesions of the nucleus basalis magnocellularis. Starting two weeks after the lesion, cytochrome c (0.3 micrograms/rat/day) or 0.01, 0.1, 1 or 10 micrograms/rat/day human recombinant nerve growth factor (NGF) was infused into the lateral ventricle. The highest dose of NGF reduced the weight gain of the animals. Six weeks, but not two weeks of treatment with 10 micrograms/rat/day NGF increased choline acetyltransferase (ChAT) activity in the frontal cortex, parietal cortex and hippocampus, predominantly on the side of the ventricular cannula. The 1 microgram/rat/day dose only increased ChAT activity in the frontal cortex on the infused side. Six weeks of treatment with 10 micrograms/rat/day NGF increased the size, but not the number of NGF-receptor-immunoreactive neurons in the nucleus basalis. This treatment did not affect the levels of dopamine, norepinephrine and serotonin in any of the brain regions studied. These data suggest that prolonged treatment with relatively high doses of NGF is necessary to increase ChAT activity in cortical regions of nucleus basalis-lesioned rats. This treatment will also increase ChAT activity in the intact septohippocampal system, but does not affect the levels of several non-cholinergic neurotransmitters.