Reindl J D, Rowan K, Carey A N, Peng X, Neumeyer J L, McLaughlin J P
Department of Psychology, Northeastern University, Boston, MA 02115, USA.
Pharmacology. 2008;81(3):229-35. doi: 10.1159/000112867. Epub 2008 Jan 7.
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.
先前的研究表明，κ阿片受体（KOR）拮抗剂可减少应激和抑郁样行为。我们推测，给予一种新型阿片类混合激动剂/拮抗剂（其在KOR上具有拮抗剂活性）将减轻强迫游泳应激（FSS）诱导的不动行为，这是一种抑郁样行为的动物模型。在用分级剂量的新型二价吗啡喃化合物二盐酸双（N-环丁基甲基吗啡喃-3-基）癸二酸酯（MCL-144B）预处理后，C57Bl/6J小鼠接受了抗伤害感受和重复的FSS测试。MCL-144B表现出剂量和时间依赖性的抗伤害感受以及KOR介导的拮抗作用。为支持该假设，在强迫游泳试验中，用MCL-144B预处理可剂量依赖性地减轻应激诱导的抗伤害感受和不动行为。
