Kojima_1998_Gen.Pharmacol_31_297

1. The purpose of this study was to examine whether NIK-247 can, by itself, induce long-lasting changes in synaptic efficacy in the hippocampus. Population spikes evoked by electrical stimulation of the stratum radiatum were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. 2. NIK-247 at 1 x 10(-7) - 1 x 10(-5) M dose dependently increased the amplitude of these spikes. The increase in population spikes by NIK-247 outlasted, for 2 hr, its presence. In addition, the increase in population spikes recovered to 2 hr after washout of NIK-247. Therefore, it was concluded that NIK-247 induced long-term potentiation (LTP) by itself. However, tacrine and physostigmine at 1 x 10(-7) - 1 x 10(-5) M did not increase the amplitude of population spikes and did not induce LTP by themselves. 3. The increase in amplitude of population spikes induced by NIK-247 was completely blocked sensitively by atropine (IC50 = 4.3 x 10(-8)M) but insensitively by pirenzepine (IC50 = 9.1 x 10(-7) M). Carbachol also increased the amplitude of population spikes in the presence of pirenzepine. 4. These findings indicate that the LTP induced by NIK-247 is due to its M2 muscarinic agonistic effect in the CA1 region of the rat hippocampus. It is expected that NIK-247 may be useful for the treatment of Alzheimer disease.