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

Eur J Pharmacol. 2007 Aug 13;569(1-2):84-9. doi: 10.1016/j.ejphar.2007.05.007. Epub 2007 May 13.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / administration & dosage
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology
  • Behavior, Animal / drug effects
  • Cocaine-Related Disorders / physiopathology*
  • Cocaine-Related Disorders / psychology
  • Conditioning, Psychological / drug effects*
  • Dynorphins / administration & dosage
  • Dynorphins / 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
  • Stress, Psychological / physiopathology
  • Stress, Psychological / prevention & control
  • Swimming / psychology
  • Time Factors

Substances

  • Analgesics, Non-Narcotic
  • Receptors, Opioid, kappa
  • arodyn
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Dynorphins