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.
Carey
A N
AN
Department of Psychology, Northeastern University, Boston, MA 02115, USA.
Borozny
K
K
Aldrich
J V
JV
McLaughlin
J P
JP
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D017473:Receptors, Opioid, kappa; C470200:arodyn; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins