title: Antidepressant-like effects of the novel kappa opioid antagonist MCL-144B in the forced-swim test.
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.
authors.affiliation: Department of Psychology, Northeastern University, Boston, MA 02115, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Reindl
authors.forename: K
authors.initials: K
authors.lastname: Rowan
authors.forename: A N
authors.initials: AN
authors.lastname: Carey
authors.forename: X
authors.initials: X
authors.lastname: Peng
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: J P
authors.initials: JP
authors.lastname: McLaughlin
mesh_terms: D000473:Alkanes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007103:Immobilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009019:Morphinans / Q000008:administration & dosage / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000188:drug therapy*; D013550:Swimming; D013997:Time Factors
chemical_list: D000473:Alkanes; D000928:Antidepressive Agents; D009019:Morphinans; D017473:Receptors, Opioid, kappa; C528102:bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride