Spinal kappa-opioid system plays an important role in suppressing morphine withdrawal syndrome in the rat.
To explore the possible involvement of spinal kappa-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 microg) or its antagonist nor-binaltorphimine (nor-BNI, 1.25-5 microg), 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.
Cui
C L
CL
Neuroscience Research Institute, Peking University, 38 Xue-Yuan Road, 100083, PR, Beijng, China.
Wu
L Z
LZ
Han
J S
JS
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine