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Journal of Pharmacology and Experimental Therapeutics

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OtherBEHAVIORAL PHARMACOLOGY

Discriminative Stimulus Effects of a Cocaine/Heroin “Speedball” Combination in Rhesus Monkeys

S. Stevens Negus, Michael B. Gatch and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics June 1998, 285 (3) 1123-1136;
S. Stevens Negus
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Nancy K. Mello
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Abstract

Cocaine and heroin often are abused together in a combination known as a “speedball,” but relatively little is known about ways in which cocaine and heroin may interact to modify each other’s abuse-related effects. The present study evaluated the discriminative stimulus effects of a speedball combination of cocaine and heroin. Three rhesus monkeys were trained to discriminate vehicle from a 10:1 ratio of cocaine (0.4 mg/kg) in combination with heroin (0.04 mg/kg). Both cocaine alone and heroin alone substituted completely for the cocaine/heroin combination, although cocaine and heroin were more potent when administered together than when administered alone. Combined pretreatment with the dopamine antagonist flupenthixol and the opioid antagonist quadazocine dose-dependently antagonized the discriminative stimulus effects of the cocaine/heroin combination, but pretreatment with either antagonist alone was less effective. These findings suggest that either cocaine or heroin alone was sufficient to substitute for the cocaine/heroin training combination. To characterize the discriminative stimulus properties of this speedball more fully, a series of cocaine-like and heroin-like agonists were studied in substitution tests. The indirect dopamine agonists CFT, amphetamine and bupropion and the mu opioid agonists alfentanil, fentanyl and morphine produced high levels of speedball-appropriate responding. However, the indirect dopamine agonist GBR12909, the D1 dopamine agonist SKF82958, the D2 dopamine agonist quinpirole and the partial mu opioid agonist nalbuphine did not substitute for the cocaine/heroin combination. Because these compounds produce discriminative stimulus effects similar to either cocaine ormu opioid agonists alone, these findings suggest that the discriminative stimulus effects of the cocaine/heroin combination do not overlap completely with the effects of cocaine and heroin alone. Finally, a series of compounds that produce partial or no substitution for cocaine or mu agonists alone also did not substitute for the cocaine/heroin combination, which indicates that the discriminative stimulus effects of the combination were pharmacologically selective. Taken together, these findings suggest that a combination of cocaine and heroin produces a pharmacologically selective discriminative stimulus complex that includes aspects of both component drugs.

Footnotes

  • Send reprint requests to: S. Stevens Negus, Alcohol and Drug Abuse Research Center, Harvard Medical School; McLean Hospital, 115 Mill St., Belmont, MA 02178-9106.

  • ↵1 These studies were supported in part by DA07252, P50-DA04059 and K05-DA00101 from the National Institute on Drug Abuse, National Institutes of Health.

  • Abbreviation:
    CFT
    (−)-3-β-(4-fluorophenyl)tropan-2-β-carboxylic acid methyl ester tartrate
    • Received October 31, 1997.
    • Accepted February 23, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 3
1 Jun 1998
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OtherBEHAVIORAL PHARMACOLOGY

Discriminative Stimulus Effects of a Cocaine/Heroin “Speedball” Combination in Rhesus Monkeys

S. Stevens Negus, Michael B. Gatch and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1123-1136;

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OtherBEHAVIORAL PHARMACOLOGY

Discriminative Stimulus Effects of a Cocaine/Heroin “Speedball” Combination in Rhesus Monkeys

S. Stevens Negus, Michael B. Gatch and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1123-1136;
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