THE BEHAVIORAL-EFFECTS OF HEPTYLPHYSOSTIGMINE ON RATS LESIONED IN THENUCLEUS BASALIS

The time course and dose dependence of acetylcholinesterase inhibition in three regions of brain were measured for the long-acting physostig mine derivative, heptylphysostigmine (HP). Behavioral studies were per formed on rats lesioned with ibotenic acid in the nucleus basalis magn ocellularis (nBM) using doses of HP that inhibit cholinesterase activi ty 20%, 40%, and 60% 2 h after injection. Spatially-cued learning and memory were tested in the water maze. Lesioned animals that received h igher doses of HP showed a trend towards improvement in the acquisitio n of this task, but this was not statistically significant. Swimming s peed was reduced in the group receiving the highest dose of HP in comp arison with a lower dose. The acoustic startle response was diminished in all groups given HP in comparison with both lesioned and sham-lesi oned saline-injected controls. Open field activity was slightly enhanc ed 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 spontan eous, stressed, or reflexive activity, although an effect on the spati al learning deficit produced by an ibotenic acid lesion of the nucleus basalis was not detected.