title: A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.
abstract: Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3 mg/kg buprenorphine and 3.0 mg/kg naltrexone was aversive. A combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3 mg/kg cocaine, drug prime was 3 mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5 mg/kg morphine, drug prime was 1.25 mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, UK.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Cordery
authors.forename: Alistair
authors.initials: A
authors.lastname: Taverner
authors.forename: Irna E
authors.initials: IE
authors.lastname: Ridzwan
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
authors.forename: M Begoña
authors.initials: MB
authors.lastname: Delgado-Charro
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D002047:Buprenorphine; D009271:Naltrexone; D009020:Morphine; D003042:Cocaine