Antidepressant-like effects of the novel kappa opioid antagonist MCL-144B in the forced-swim test

作者：Reindl J D; Rowan K; Careya A X; Peng X; Neumeyer J L; McLaughlin J P^*

来源：Pharmacology, 2008, 81(3): 229-235.

DOI：10.1159/000112867

• mixed agonist/antagonist
• kappa receptors
• opioids
• stress
• depression

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. C57BI/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.

• 出版日期2008
• 单位东北大学