Physostigmine reverses memory deficits produced by pretraining electrical stimulation of the dorsal hippocampus in mice.

The aim of the present experiments was to test the validity of the hypothesis that presynaptic cholinergic activity has a functional significance for memory formation. The results show that electrical stimulation of the dorsal hippocampus delivered before learning in BALB/c mice which induces a decrease of about 40% in hippocampal choline acetyltransferase (ChAT) activity at the time of learning results in deficits in retention scores in two appetitive learning tasks (operant conditioning in the Skinner box or a spatial memory task using a 4-hole board). In both behavioral tasks intraventricular injection of 1 microgram of physostigmine 20 min before the acquisition session reverses the disruptive effect of pretraining hippocampal stimulation. Our results seem to indicate that the memory deficits produced by pretraining electrical stimulation of the hippocampus result from both a decrease in ChAT activity and a corresponding reduction of acetylcholine availability in the hippocampal formation.