Pharmacological Characterization of the Ameliorating Effect on Learning and Memory Impairment and Antinociceptive Effect of Kt-95 in Mice.
From: Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Behavioural brain research
- Publish Date: Feb 2006
- ISSN: 0166-4328
- Volume: 167
- Issue: 2
- Pages: 219-25
- Medium: Print
- Language: English
- Citation (JAMA): Hiramatsu Masayuki, Mizuno Natsuko, Kanematsu Ken, et al. Pharmacological Characterization of the Ameliorating Effect on Learning and Memory Impairment and Antinociceptive Effect of Kt-95 in Mice.. Behav. Brain Res. Feb 2006;167:219-25
Abstract
3-Acetoxy-6beta-acetylthio-10-oxo-N-cyclopropylmethyl-dihydronormorphine (KT-95) is a synthesized compound that binds to mu-, delta- and kappa-opioid receptors in vitro. KT-95 induces analgesia and this effect is antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. We have reported that kappa-opioid receptor agonists improve impairment of learning and memory in mice and/or rats. In this study, the effects of KT-95 were investigated in an acetic acid-induced writhing test and scopolamine-induced memory impairment test using spontaneous alternation performance in a Y-maze and a step-down type passive avoidance test. Male ddY mice were treated with KT-95 (0.24-2.35 micromol/kg, s.c.) 30 min before the behavioral test. In the writhing test, the antinociceptive effect of KT-95 (2.35 micromol/kg) was completely antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but not by naloxone (3.05 micromol/kg, s.c.). KT-95 significantly improved the impairment of spontaneous alternation induced by scopolamine (1.65 micromol/kg, s.c.). The ameliorating effect of KT-95 was not antagonized by nor-BNI, but was almost completely antagonized by a selective sigma-receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100, 2.6 micromol/kg, i.p.). KT-95 also significantly improved scopolamine-induced learning and memory impairment in the passive avoidance test, although the effect was partial. Administration of KT-95 itself induced impairment of learning and memory. KT-95-induced impairment was not antagonized by naloxone, naltrindole, nor-BNI or NE-100 indicating that this impairment was not because of opioid receptor stimulation. These results suggested that although the KT-95-induced antinociceptive effect was mediated by kappa-opioid receptors, the KT-95-induced improvement in scopolamine-induced impairment of memory was mediated mainly via sigma-receptors and partially by kappa-opioid receptors.
Mesh Headings (Keywords): Animals, Avoidance Learning, Dose-Response Relationship, Drug, Drug Interactions, Male, Maze Learning, Memory, Mice, Morphine Derivatives, Muscarinic Antagonists, Nootropic Agents, Pain Threshold, Receptors, Opioid, kappa, Receptors, sigma, Scopolamine
Check for Full Text / PubMed Unique Identifier (PMID): 16223533
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