Abstract
The opiate withdrawal induced by administration of naloxone to morphine-dependent mice correlates with an increment of calcium- dependent nitric oxide synthase (NOS) activity in the cerebellum. L-NAME, an irreversible competitive inhibitor of NOS (0.5, 5, 25, 50 mg/kg) injected sc. 45 min. prior to naloxone significantly reduced the number of escape jumps and other motor symptoms of abstinence. In addition, L-NAME also decreased NOS activity in cerebellum. L-arginine, but not D-arginine, when coadministered with L-NAME, prevented both the inhibition of NOS activity and the reduction of withdrawal symptoms induced by L-NAME in morphine-withdrawn animals. These results demonstrate a hyperactivity of the L-arginine: NO pathway in opiate withdrawal and suggests the possibility of a therapeutic use of NOS inhibitors in this state.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arginine / administration & dosage
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Cerebellum / drug effects
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Cerebellum / enzymology*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Synergism
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Injections, Subcutaneous
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Male
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Mice
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Morphine Dependence / enzymology
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NG-Nitroarginine Methyl Ester
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Naloxone / administration & dosage
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Naloxone / pharmacology*
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Naloxone / therapeutic use
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Narcotic Antagonists / administration & dosage
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Narcotic Antagonists / pharmacology*
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Narcotic Antagonists / therapeutic use
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Narcotics / metabolism*
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism*
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Stereoisomerism
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Substance Withdrawal Syndrome / drug therapy
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Substance Withdrawal Syndrome / enzymology*
Substances
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Narcotic Antagonists
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Narcotics
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Nitric Oxide
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Naloxone
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Arginine
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Nitric Oxide Synthase
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NG-Nitroarginine Methyl Ester