title: Interactions between the reinforcing effects of cocaine and heroin in a drug-vs-food choice procedure in rhesus monkeys: a dose-addition analysis.
abstract: BACKGROUND
  Concurrent abuse of cocaine and heroin is a common form of polydrug abuse, but the interactions between the reinforcing effects of cocaine and heroin are poorly understood. Dose-addition analysis is a tool for the quantitative assessment of drug interactions, but this analysis has not been applied to evaluation of the reinforcing effects of cocaine and heroin.
  
  
  OBJECTIVE
  To evaluate interactions between the reinforcing effects of cocaine and heroin using dose-addition analysis.
  
  
  METHODS
  Rhesus monkeys were trained under a concurrent-choice schedule of food delivery (1 gm pellets) and drug injections (cocaine or heroin, 0-0.1 mg kg(-1) injection(-1)). Full dose-effect curves were determined for cocaine alone and heroin alone. Subsequently, full dose-effect curves were determined for three fixed-proportion mixtures of cocaine and heroin (fixed proportions of 1:3.2, 1:1 and 3.2:1 cocaine/heroin). Dose-addition analysis was used to assess whether cocaine/heroin interactions were super-additive, additive, or sub-additive.
  
  
  RESULTS
  Cocaine, heroin, and all cocaine/heroin mixtures maintained dose-dependent and monotonic increases in drug choice and dose-dependent decreases in response rates. Choice dose-effect curves for cocaine/heroin mixtures were shifted to the left of dose-effect curves for cocaine or heroin alone, and dose-addition analysis indicated that cocaine/heroin interactions on drug choice were sub-additive or additive. Cocaine/heroin interactions on response-rate measures were also sub-additive or additive.
  
  
  CONCLUSIONS
  These results confirm that mixtures of cocaine and heroin produce reinforcing effects in rhesus monkeys; however, cocaine/heroin interactions were only or sub-additive or additive. Thus, these results do not support the hypothesis that simultaneously delivered cocaine and heroin produces super-additive reinforcing effects.
authors.affiliation: Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. negus@mclean.harvard.edu
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology; D002755:Choice Behavior / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D012054:Reinforcement, Psychology; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D003932:Heroin; D003042:Cocaine