title: Assessment of the effects of contingent histamine injections on the reinforcing effectiveness of cocaine using behavioral economic and progressive-ratio designs.
abstract: BACKGROUND
  Recent research has demonstrated that the drug, histamine, can function as a punisher of cocaine self-administration. However, little is known about how drug punishers affect the maximum reinforcing effectiveness of drugs as reinforcers.
  
  
  OBJECTIVE
  The goal of the present study was to determine if histamine, when self-administered as a mixture with cocaine, could reduce cocaine's maximum reinforcing effectiveness using two procedures designed for measuring reinforcing effectiveness.
  
  
  METHODS
  In the first experiment, rhesus monkeys were allowed to self-administer cocaine (0.1 mg/kg/inj) alone or as a mixture with histamine (0.012-0.05 mg/kg/inj) in a behavioral economic design. In the second experiment, monkeys were allowed to self-administer cocaine alone (0.006-0.56 mg/kg/inj) or as a mixture with histamine (0.025-0.1 mg/kg/inj) under a progressive-ratio schedule of reinforcement.
  
  
  RESULTS
  In Experiment 1, histamine decreased the reinforcing effectiveness of cocaine in a dose-dependent manner as evidenced by increases in cocaine's demand elasticity with increases in histamine dose. In Experiment 2, histamine decreased cocaine's potency and effectiveness as a reinforcer in a dose-dependent manner as indicated by rightward and downward shifts, respectively, in the dose-response functions.
  
  
  CONCLUSIONS
  The reinforcing effectiveness of cocaine can be reduced by contingent self-administration of histamine. These results indicate that combining drug punishers with drug reinforcers reduces the maximum reinforcing effect of the drug reinforcer, which suggests a use for drug punishers as a deterrent to drug abuse (e.g., as mixtures with prescription medications with abuse potential).
authors.affiliation: Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, 39216, USA, kfreeman@umc.edu.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Freeman
authors.forename: Brian C
authors.initials: BC
authors.lastname: McMaster
authors.forename: Peter G
authors.initials: PG
authors.lastname: Roma
authors.forename: William L
authors.initials: WL
authors.lastname: Woolverton
mesh_terms: D000818:Animals; D002408:Catheters, Indwelling; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D060909:Economics, Behavioral; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D017442:Histamine Agonists; D006632:Histamine; D003042:Cocaine