Spinal kappa-opioid system plays an important role in suppressing morphine withdrawal syndrome in the rat

To explore the possible involvement of spinal K-opioid receptor in modulating morphine withdrawal syndrome, rats were made dependent on morphine by multiple injections of morphine HCl for 5 days. They were then given intrathecal administration (i.t.) of a kappa -opioid receptor agonist trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]-benzenacetamide hydrochloride (U-50,488H, 2.5-10 mug) or its antagonist nor-binaltorphimine (nor-BNI, 1.25-5 mug), followed by intraperitoneal administration (i.p.) of naloxone (0.5 mg/kg), and the withdrawal syndrome was scored for 60 min. U-50,488H produced a dose-dependent suppression, whereas nor-BNI a dose-dependent potentiation in withdrawal syndrome. The latter result implies that an endogenous kappa receptor agonist, most probably dynorphin, exerts a tonic suppressive effect on morphine syndrome at spinal level. (C) 2000 Elsevier Science Ireland Ltd. AII rights reserved.