SIGMA-RECEPTOR LIGANDS (-SKF10,047 AND SA4503 IMPROVE DIZOCILPINE-INDUCED SPATIAL MEMORY DEFICITS IN RATS())

This study examined the effects of the sigma receptor ligands (+)-N-al lylnormetazocine ((+)-SKF10,047) and 4-dimethoxyphenethyl)-4-(3-phenyl propyl)piperazine dihydrochloride (SA4503) on dizocilpine-induced impa irment of working and reference memory in a radial arm maze task in ra ts. Dizocilpine, a non-competitive NMDA receptor antagonist, significa ntly impaired both reference and working memory, an effect which was a ccompanied by ataxia and impairment of food intake. The dizocilpine-in duced impairment of reference memory was dose-dependently attenuated b y (+)SKF10,047 and SA4503. SA4503 also attenuated the dizocilpine-indu ced working memory impairment, although (+)-SKF10,047 had no effect. N either a receptor ligand affected the behavioral symptoms such as atax ia and impairment of food intake induced by dizocilpine. The ameliorat ing effects of both (+)-SKF10,047 and SA4503 on dizocilpine-induced sp atial memory impairment were completely antagonized by a a, receptor a ntagonist methoxy-3-(2-phenyl]-ethylamine-monohydrochloride. These res ults suggest that the interaction of sigma(1) receptors with MDA recep tors modulates spatial memory in rats. (C) 1998 Elsevier Science B.V. All rights reserved.