S.08.01 Modulators of NMDA receptors

Abstract

Senda, T., K. Matsuno, T. Kobayashi and S. Mita. Reduction of the scopolamine-induced impairment of passive-avoidance performance by σ receptor agonist in mice. Physiol Behav 61(2) 257–264, 1997.—We examined the ameliorating effects of several σ receptor agonists on scopolamine-induced memory impairment in mice. Scopolamine was administered IP 30 min before the training session. Each σ receptor agonist was administered 60 min before or immediately after the training session, or 60 min before the retention test in the passive-avoidance performance experiments. (+)-N-Allylnormetazocine ((+)-SKF-10,047), a prototype σ1 receptor agonist, showed an ameliorating effect on the scopolamine-induced memory impairment in these 3 administration schedules, and (−)-SKF-10,047, a stereoisomer with low affinity for the σ1 receptor subtype, failed to reduce this memory impairment in mice. In addition, 1,3-di(2-tolyl)guanidine (DTG) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperizine ((+)-3-PPP), nonselective σ receptor agonists, did not affect this memory impairment. Physostigmine, an acetylcholinesterase (AChE) inhibitor, alleviated the scopolamine-induced memory impairment in all these drug administration schedules. In addition, (+)-SKF-10,047-induced antiamnesic effect was antagonized by the concurrent administration of haloperidol, a σ receptor antagonist, or N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride (NE-100), a selective σ1 receptor antagonist. These findings indicate that the σ1 receptor agonist has ameliorating effects on all phases of learning and memory processes. This profile of σ1 receptor agonist is similar to that of an AChE inhibitor.