Antidepressant-Like Effects of the Novel Kappa Opioid Antagonist MCL-144B in the Forced-Swim Test
Previous studies have demonstrated that kappa opioid receptor (KOR) antagonists reduce stress- and depression-like behaviors. We hypothesized that administration of a novel opioid mixed agonist/antagonist capable of antagonist activity at the KOR would attenuate forced-swim stress (FSS)-induced immo...
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| Published in | Pharmacology Vol. 81; no. 3; pp. 229 - 235 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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Basel, Switzerland
S. Karger AG
01.01.2008
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| Abstract | Previous studies have demonstrated that kappa opioid receptor (KOR) antagonists reduce stress- and depression-like behaviors. We hypothesized that administration of a novel opioid mixed agonist/antagonist capable of antagonist activity at the KOR would attenuate forced-swim stress (FSS)-induced immobility, an animal model of depression-like behavior. C57Bl/6J mice were exposed to antinociceptive and repeated FSS testing after pretreatment with a graded dose of a novel bivalent morphinan compound, bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride (MCL-144B). MCL-144B demonstrated dose- and time-dependent antinociception and KOR-mediated antagonism. In support of the hypothesis, pretreatment with MCL-144B dose-dependently attenuated stress-induced antinociception and immobility in the forced-swim test. |
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| AbstractList | Previous studies have demonstrated that kappa opioid receptor (KOR) antagonists reduce stress- and depression-like behaviors. We hypothesized that administration of a novel opioid mixed agonist/antagonist capable of antagonist activity at the KOR would attenuate forced-swim stress (FSS)-induced immobility, an animal model of depression-like behavior. C57Bl/6J mice were exposed to antinociceptive and repeated FSS testing after pretreatment with a graded dose of a novel bivalent morphinan compound, bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride (MCL-144B). MCL-144B demonstrated dose- and time-dependent antinociception and KOR-mediated antagonism. In support of the hypothesis, pretreatment with MCL-144B dose-dependently attenuated stress-induced antinociception and immobility in the forced-swim test. Previous studies have demonstrated that kappa opioid receptor (KOR) antagonists reduce stress- and depression-like behaviors. We hypothesized that administration of a novel opioid mixed agonist/antagonist capable of antagonist activity at the KOR would attenuate forced-swim stress (FSS)-induced immobility, an animal model of depression-like behavior. C57Bl/6J mice were exposed to antinociceptive and repeated FSS testing after pretreatment with a graded dose of a novel bivalent morphinan compound, bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride (MCL-144B). MCL-144B demonstrated dose- and time-dependent antinociception and KOR-mediated antagonism. In support of the hypothesis, pretreatment with MCL-144B dose-dependently attenuated stress-induced antinociception and immobility in the forced-swim test. Copyright © 2008 S. Karger AG, Basel [PUBLICATION ABSTRACT] |
| Author | Peng, X. Rowan, K. Reindl, J.D. Neumeyer, J.L. Carey, A.N. McLaughlin, J.P. |
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| Keywords | Depression Mixed agonist/antagonist Stress Kappa receptors Opioids |
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| License | Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2008 S. Karger AG, Basel. |
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| SubjectTerms | Alkanes - administration & dosage Alkanes - pharmacology Animals Antidepressive Agents - administration & dosage Antidepressive Agents - pharmacology Depression - drug therapy Disease Models, Animal Dose-Response Relationship, Drug Immobilization Male Mice Mice, Inbred C57BL Morphinans - administration & dosage Morphinans - pharmacology Original Paper Receptors, Opioid, kappa - antagonists & inhibitors Stress, Psychological - drug therapy Swimming Time Factors |
| Title | Antidepressant-Like Effects of the Novel Kappa Opioid Antagonist MCL-144B in the Forced-Swim Test |
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