u-50488 and Depressive-Disorder

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.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics, Non-Narcotic; Animals; Benzomorphans; Brain; Depression; Depressive Disorder; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Helplessness, Learned; Male; Mice; Narcotic Antagonists; Opioid Peptides; Receptors, Opioid, kappa