S Stevens Negus1. 1. Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. negus@mclean.harvard.edu
Abstract
RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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. OBJECTIVES: 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: James E Smith; Conchita Co; Michael D Coller; Scott E Hemby; Thomas J Martin Journal: Neuropsychopharmacology Date: 2006-01 Impact factor: 7.853
Authors: Tommy Gunawan; Yosuke Hachiga; Christopher S Tripoli; Alan Silberberg; David N Kearns Journal: Psychopharmacology (Berl) Date: 2020-01-29 Impact factor: 4.530