Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.

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.
Authors	A N Carey, K Borozny, J V Aldrich, J P McLaughlin
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 569 Issue 1-2 Pg. 84-9 (Aug 13 2007) ISSN: 0014-2999 [Print] Netherlands
PMID	17568579 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Analgesics, Non-Narcotic Receptors, Opioid, kappa arodyn 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer Dynorphins
Topics	3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer (administration & dosage, pharmacology) Analgesics, Non-Narcotic (administration & dosage, pharmacology) Animals Behavior, Addictive (physiopathology, psychology) Behavior, Animal (drug effects) Cocaine-Related Disorders (physiopathology, psychology) Conditioning, Psychological (drug effects) Dynorphins (administration & dosage, pharmacology) Extinction, Psychological (drug effects) Female Hot Temperature (adverse effects) Injections, Intraventricular Male Mice Mice, Inbred C57BL Pain Measurement (methods) Pain Threshold (drug effects) Reaction Time (drug effects) Receptors, Opioid, kappa (antagonists & inhibitors) Stress, Psychological (etiology, physiopathology, prevention & control) Swimming (psychology) Time Factors

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