Pharmacological characterization of the ameliorating effect on short-term memory impairment and antinociceptive effect of KT-90 in mice

• Published in: Behavioural brain research 2005-05, Vol.160 (2), p.374-381
• Main Authors: Hiramatsu, Masayuki, Hoshino, Takashi, Kanematsu, Ken
• Format: Article
• Language: English
• Subjects: Animal; Animals; Anisoles - pharmacology; Antinociceptive effect; Antipsychotic Agents - pharmacology; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; KT-90; Learning. Memory; Male; Maze Learning - drug effects; Memory; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory, Short-Term - drug effects; Mice; Morphine Derivatives - therapeutic use; Narcotic Antagonists - pharmacology; Neurotransmission and behavior; Pain - drug therapy; Pain Measurement - methods; Propylamines - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Opioid - agonists; Scopolamine Hydrobromide; Short-term memory; Spontaneous alternation; Statistics, Nonparametric; κ-Opioid receptor; σ Receptor
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2005.01.003

(−)-3-Acetyl-6β-acetylthio- N-cyclopropylmethyl-normorphine (KT-90) is a synthesized compound that binds to μ-, δ- and κ-opioid receptors in vitro. KT-90 induces analgesia in the tail-flick test and this effect is antagonized by nor-BNI, a selective κ-opioid receptor antagonist. However, lower doses of KT-90 antagonize morphine-induced analgesia. We reported that κ-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 μmol/kg, s.c.) 30 min before the behavioral test. KT-90 (0.07–2.35 μmol/kg, s.c.) was injected 30 min before testing. In the writhing test, the antinociceptive effect of KT-90 (0.71 μmol/kg) was completely antagonized by a selective μ-opioid receptor antagonist, β-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 δ-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 σ receptor antagonist, NE-100 (2.6 μmol/kg, i.p.). These results suggested that the KT-90-induced antinociceptive effect was mediated by μ- and partially by κ-opioid receptors, and the KT-90-induced improvement in scopolamine-induced impairment of spontaneous alternation was mediated mainly via σ receptors.