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

To explore the possible involvement of spinal κ-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 κ-opioid receptor agonist trans-3,4-dichloro- N-methyl- N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzenacetamide hydrochloride (U-50,488H, 2.5–10 μg) or its antagonist nor-binaltorphimine (nor-BNI, 1.25–5 μg), 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.