title: The mu/kappa agonist nalbuphine attenuates sensitization to the behavioral effects of cocaine.
abstract: Sensitization refers to an increase in sensitivity to a drug and is believed to play a role in the etiology of substance use disorders. The purpose of the present study was to evaluate the ability of the mixed mu/kappa agonist nalbuphine to modulate sensitization to the locomotor and positive reinforcing effects of cocaine. Rats were habituated to a locomotor activity chamber and treated with saline (1.0 ml/kg, ip), cocaine (10 mg/kg, ip), or cocaine+nalbuphine (10 mg/kg, ip) every day for 10 days. Following locomotor activity testing, rats were implanted with intravenous catheters and cocaine self-administration was examined on fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Rats treated with cocaine exhibited a progressive increase in locomotor activity over the 10-day treatment period, and this effect was significantly reduced in rats treated with cocaine+nalbuphine. In self-administration tests, rats treated with cocaine exhibited significantly higher levels of responding at a threshold dose of cocaine (0.03 mg/kg/infusion) on both FR and PR schedules than rats treated with saline. This increase in responding at a threshold dose of cocaine was blocked completely in rats treated with cocaine+nalbuphine. These data suggest that nalbuphine attenuates the development of sensitization to the behavioral effects of cocaine.
authors.affiliation: Department of Psychology, Davidson College, Davidson, NC 28035, USA. masmith@davidson.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: K T
authors.initials: KT
authors.lastname: Cole
authors.forename: J C
authors.initials: JC
authors.lastname: Iordanou
authors.forename: D C
authors.initials: DC
authors.lastname: Kerns
authors.forename: P C
authors.initials: PC
authors.lastname: Newsom
authors.forename: G W
authors.initials: GW
authors.lastname: Peitz
authors.forename: K T
authors.initials: KT
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D004361:Drug Tolerance; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009266:Nalbuphine / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D003042:Cocaine; D009266:Nalbuphine