Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / therapeutic use*
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Analgesics, Non-Narcotic / pharmacology
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Analgesics, Non-Narcotic / therapeutic use*
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Analgesics, Opioid / adverse effects*
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Animals
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Male
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Morphine / adverse effects*
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Naltrexone / analogs & derivatives
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Rats
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Rats, Wistar
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Receptors, Opioid, kappa* / drug effects
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Receptors, Opioid, kappa* / physiology
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Substance Withdrawal Syndrome / drug therapy*
Substances
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Analgesics, Non-Narcotic
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Analgesics, Opioid
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Narcotic Antagonists
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Receptors, Opioid, kappa
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norbinaltorphimine
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Naltrexone
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Morphine