Involvement of kappa-opioid and sigma receptors in short-term memory in mice.
Kappa-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. sigma 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 micromol/kg, subcutaneously (s.c.)) and (+)-SKF10,047 (0.10-1.02 micromol/kg, s.c.) 25 min before the Y-maze test improved the impairment of spontaneous alternation induced by scopolamine (1.65 micromol/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 sigma receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100), and a selective kappa-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 kappa-opioid and sigma receptors-mediated mechanisms.
Hiramatsu
Masayuki
M
Department of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Meijo University, Nagoya 468-8502, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Hoshino
Takashi
T
Kameyama
Tsutomu
T
Nabeshima
Toshitaka
T
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma