Spinal kappa-opioid system plays an important role in suppressing morphine withdrawal syndrome in the rat
Cai-Lian Cui, Liu-Zhen Wu, Ji-Sheng Han*
Neuroscience Research Institute, Peking University, 38 Xue-Yuan Road, Beijng 100083, PR China
Received 5 June 2000; received in revised form 17 October 2000; accepted 19 October 2000
Abstract
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 k-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzenacetamide hydrochloride (U-50,488H, 2.5±10 mg) or its antagonist nor-binaltorphimine (nor-BNI, 1.25±5 mg), 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. q 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: k-Opioid receptor; Morphine withdrawal syndrome; Trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzenacetamide hydrochloride; Nor-binaltorphimine; Spinal cord; Naloxone
Neuroscience Letters 295 (2000) 45±48
