κ-Opioid receptor agonists, trans-(±)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulfonate (U-50,488H) and dynorphin A-(1-13), improve impairments of learning and memory in mice and rats. σ Receptor agonists, (+)-N-allylnormetazocine ((+)-SKF10,047) and 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (SA4503), also reverse learning and memory impairment in various animal models. However, the mechanisms underlying these effects are not well understood. In the present study, the effect of coadministration of U-50,488H and (+)-SKF10,047 on scopolamine-induced memory impairment was investigated in mice using spontaneous alternation performance in a Y-maze. U-50,488H (0.21-2.15 μmol/kg, subcutaneously (s.c.)) and (+)-SKF10,047 (0.10-1.02 μmol/kg, s.c.) 25 min before the Y-maze test improved the impairment of spontaneous alternation induced by scopolamine (1.65 μmol/kg, s.c.). When U-50,488H and (+)-SKF10,047 were coadministered, no additive effect was observed. Furthermore, the ameliorating effects of U-50,488H and (+)-SKF10,047 were not antagonized by a selective σ receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100), and a selective κ-opioid receptor antagonist, nor-binaltorphimine, respectively. These results suggest that the mechanisms underlying the ameliorating effects on memory impairment are independent and no direct modulation exists in κ-opioid and σ receptors-mediated mechanisms.
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