Reduction of the scopolamine-induced impairment of passive-avoidance performance by sigma receptor agonist in mice

Author(s): Matsuno, K., Kobayashi, T., Mita, S.

Journal/Book: Physiol Behav. 1997; 61: The Boulevard, Langford Lane, Kidlington, Oxford, England OX5 1GB. Pergamon-Elsevier Science Ltd. 257-264.

Abstract: We examined the ameliorating effects of several a receptor agonists on scopolamine induced memory impairment in mice. Scopolamine was administered IP 30 min before the training session. Each sigma 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-10,037), a prototype sigma(1) 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 sigma(1) 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 a 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 sigma receptor antagonist, or N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride (NE-100), a selective sigma(1) receptor antagonist. These findings indicate that the sigma(1) receptor agonist has ameliorating effects on all phases of learning and memory processes. This profile of sigma(1) receptor agonist is similar to that of an AChE inhibitor.

Note: Article Matsuno K, Santen Pharmaceut Co Ltd, Cent Res Labs, New Drug Res, 3-9-19 Shimoshinjo, Osaka 533, JAPAN

Keyword(s): sigma receptor agonists; (+)-SKF-10,047; (-)-SKF-10,047; DTG; (+)-3-PPP; sigma(1) receptor subtype; scopolamine; memory impairment; passive-avoidance performance; mice; GUINEA-PIG BRAIN; EXTRACELLULAR ACETYLCHOLINE LEVEL; RAT FRONTAL-CORTEX; BINDING-SITES; BEHAVIORAL EVIDENCE; MEMORY PROCESSES; MODULATING ROLE; LIGANDS; INVOLVEMENT; TETRAHYDROAMINOACRIDINE

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