Pharmacological characterization of the ameliorating effect on short-term memory impairment and antinociceptive effect of KT-90 in mice.
(-)-3-Acetyl-6beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) is a synthesized compound that binds to mu-, delta- and kappa-opioid receptors in vitro. KT-90 induces analgesia in the tail-flick test and this effect is antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. However, lower doses of KT-90 antagonize morphine-induced analgesia. We reported that kappa-opioid receptor agonists such as U-50,488H and dynorphin A (1-13), improved scopolamine-induced impairment of learning and memory in mice and/or rats. In this study, the effects of KT-90 were investigated in an acetic acid-induced writhing test and scopolamine-induced memory impairment test using spontaneous alternation performance in a Y-maze. Male ddY mice were treated with scopolamine (1.65 micromol/kg, s.c.) 30 min before the behavioral test. KT-90 (0.07-2.35 micromol/kg, s.c.) was injected 30 min before testing. In the writhing test, the antinociceptive effect of KT-90 (0.71 micromol/kg) was completely antagonized by a selective mu-opioid receptor antagonist, beta-funaltrexamine (10.2 nmol/mouse, i.c.v.) and partially antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but it was not antagonized by a selective delta-opioid receptor antagonist, naltrindole (9.1 pmol/mouse, i.c.v.). KT-90 significantly improved the impairment of spontaneous alternation induced by scopolamine. The ameliorating effect of KT-90 was not antagonized by nor-BNI, but was almost completely antagonized by a selective sigma receptor antagonist, NE-100 (2.6 micromol/kg, i.p.). These results suggested that the KT-90-induced antinociceptive effect was mediated by mu- and partially by kappa-opioid receptors, and the KT-90-induced improvement in scopolamine-induced impairment of spontaneous alternation was mediated mainly via sigma receptors.
Hiramatsu
Masayuki
M
Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Meijo University, Nagoya, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Hoshino
Takashi
T
Kanematsu
Ken
K
D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009022:Morphine Derivatives / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D011437:Propylamines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*; D012601:Scopolamine; D018709:Statistics, Nonparametric
D000840:Anisoles; D014150:Antipsychotic Agents; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D011437:Propylamines; D011957:Receptors, Opioid; C065295:KT 90; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D012601:Scopolamine