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 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.
Reindl
J D
JD
Department of Psychology, Northeastern University, Boston, MA 02115, USA.
Rowan
K
K
Carey
A N
AN
Peng
X
X
Neumeyer
J L
JL
McLaughlin
J P
JP
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
D000473:Alkanes; D000928:Antidepressive Agents; D009019:Morphinans; D017473:Receptors, Opioid, kappa; C528102:bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride