title: Effects of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) on cocaine versus food choice and extended-access cocaine intake in rhesus monkeys.
abstract: The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse-related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self-administration under a novel procedure that featured two daily components: (1) a 2-hour 'choice' component (9:00-11:00 am) when monkeys could choose between food pellets and cocaine injections (0-0.1 mg/kg per injection, intravenous) and (2) a 20-hour 'extended-access' component (noon to 8:00 am) when cocaine (0.1 mg/kg per injection) was available under a fixed-ratio schedule to promote high daily cocaine intakes. Rhesus monkeys (n = 4) were given 14 days of exposure to the choice + extended-access procedure then treated with nor-BNI (3.2 or 10.0 mg/kg, intramuscular), and cocaine choice and extended-access cocaine intake were evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained both a dose-dependent increase in cocaine choice during choice components and a high level of cocaine intake during extended-access components. Neither 3.2 nor 10 mg/kg nor-BNI significantly altered cocaine choice or extended-access cocaine intake. In two additional monkeys, nor-BNI also had no effect on cocaine choice or extended-access cocaine intake when it was administered at the beginning of exposure to the extended-access components. Overall, these results do not support a major role for the dynorphin/KOR system in modulating cocaine self-administration under these conditions in non-human primates nor do they support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy for cocaine addiction.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Blake A
authors.initials: BA
authors.lastname: Hutsell
authors.affiliation: Chemical Biology Branch, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD, USA.
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Chemical Biology Branch, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD, USA.
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.|Institute for Drug and Alcohol Abuse Studies, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Sidney Stevens
authors.initials: SS
authors.lastname: Negus
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.|Institute for Drug and Alcohol Abuse Studies, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Matthew L
authors.identifier: http://orcid.org/0000-0003-4949-5246
authors.initials: ML
authors.lastname: Banks
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D012646:Self Administration
chemical_list: D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D003042:Cocaine
keywords: Addiction; choice; cocaine; kappa opioid receptor; nor-binaltorphimine; rhesus monkey