Effects of U-50,488H, a kappa-opioid receptor agonist, on the learned helplessness model of depression in mice.
We investigated the effects of U-50,488H, a kappa-opioid receptor agonist, on the learned helplessness model of depression in mice. Mice pre-exposed to inescapable electric footshock were treated with U-50,488H. Stimulation of the kappa-opioid receptor by U-50,488H (10 mg/kg/day, i.p.) attenuated the escape failure induced by pre-exposure to shock. This attenuation by U-50,488H was blocked by MR2266 (10 mg/kg/day, s.c.), an opioid receptor antagonist. These results suggest that the kappa-opioid system plays an important role in the learned helplessness depression in mice.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Japan. ukai@ccmfs.meijo-u.ac.jp
Suzuki
M
M
Mamiya
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006380:Helplessness, Learned; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D001575:Benzomorphans; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer