Antidepressant-Like Effects of the Novel Kappa Opioid Antagonist MCL-144B in the Forced-Swim Test

• Published in: Pharmacology Vol. 81; no. 3; pp. 229 - 235
• Main Authors: Reindl, J.D., Rowan, K., Carey, A.N., Peng, X., Neumeyer, J.L., McLaughlin, J.P.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2008
• Subjects: 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; Depression; Mixed agonist/antagonist; Stress; Kappa receptors; Opioids
• ISSN: 0031-7012; 1423-0313
• DOI: 10.1159/000112867

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.