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-allylnormetazocine ((+)-SKF10,047) and 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) on dizocilpine-induced impairment of working and reference memory in a radial arm maze task in rats. Dizocilpine, a non-competitive NMDA receptor antagonist, significantly impaired both reference and working memory, an effect which was accompanied by ataxia and impairment of food intake. The dizocilpine-induced impairment of reference memory was dose-dependently attenuated by (+)-SKF10,047 and SA4503. SA4503 also attenuated the dizocilpine-induced working memory impairment, although (+)-SKF10,047 had no effect. Neither sigma receptor ligand affected the behavioral symptoms such as ataxia and impairment of food intake induced by dizocilpine. The ameliorating effects of both (+)-SKF10,047 and SA4503 on dizocilpine-induced spatial memory impairment were completely antagonized by a sigma1 receptor antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine-mon ohydrochloride. These results suggest that the interaction of sigma1 receptors with NMDA receptors modulates spatial memory in rats.
Zou
L B
LB
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Yamada
K
K
Nabeshima
T
T
D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D018697:Nootropic Agents / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017480:Receptors, sigma / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; C101789:SA 4503; D010620:Phenazocine