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

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.