The behavioral effects of heptylphysostigmine on rats lesioned in the nucleus basalis

The time course and dose dependence of acetylcholinesterase inhibition in three regions of brain were measured for the long-acting physostigmine derivative, heptylphysostigmine (HP). Behavioral studies were performed on rats lesioned with ibotenic acid in the nucleus basalis magnocellularis (nBM) using doses of HP that inhibit cholinesterase activity 20%, 40%, and 60% 2 h after injection. Spatially-cued learning and memory were tested in the water maze. Lesioned animals that received higher doses of HP showed a trend towards improvement in the acquisition of this task, but this was not statistically significant. Swimming speed was reduced in the group receiving the highest dose of HP in comparison with a lower dose. The acoustic startle response was diminished in all groups given HP in comparison with both lesioned and sham-lesioned saline-injected controls. Open field activity was slightly enhanced by the presence of the nBM lesion. HP reduced the hyperactivity in a dose-dependent manner. Deficiencies in limb strength or coordination were not detected. These results suggest that HP may decrease spontaneous, stressed, or reflexive activity, although an effect on the spatial learning deficit produced by an ibotenic acid lesion of the nucleus basalis was not detected.