Abstract
Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / administration & dosage
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
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Analgesics, Non-Narcotic / administration & dosage
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Analgesics, Non-Narcotic / pharmacology
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Animals
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Behavior, Addictive / physiopathology
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Behavior, Addictive / psychology
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Behavior, Animal / drug effects
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Cocaine-Related Disorders / physiopathology*
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Cocaine-Related Disorders / psychology
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Conditioning, Psychological / drug effects*
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Dynorphins / administration & dosage
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Dynorphins / pharmacology*
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Extinction, Psychological / drug effects
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Female
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Hot Temperature / adverse effects
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Injections, Intraventricular
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Male
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Mice
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Mice, Inbred C57BL
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Pain Measurement / methods
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Pain Threshold / drug effects
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Reaction Time / drug effects
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Receptors, Opioid, kappa / antagonists & inhibitors*
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Stress, Psychological / etiology
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Stress, Psychological / physiopathology
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Stress, Psychological / prevention & control
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Swimming / psychology
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Time Factors
Substances
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Analgesics, Non-Narcotic
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Receptors, Opioid, kappa
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arodyn
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Dynorphins