DISCRIMINATIVE STIMULUS EFFECTS OF A COCAINE HEROIN SPEEDBALL COMBINATION IN RHESUS-MONKEYS/

Cocaine and heroin often are abused together in a combination known as a ''speedball,'' but relatively little is known about ways in which c ocaine and heroin may interact to modify each other's abuse-related ef fects. The present study evaluated the discriminative stimulus effects of a speedball combination of cocaine and heroin. Three rhesus monkey s 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 combina tion, although cocaine and heroin were more potent when administered t ogether than when administered alone. Combined pretreatment with the d opamine antagonist flupenthixol and the opioid antagonist quadazocine dose-dependently antagonized the discriminative stimulus effects of th e cocaine/heroin combination, but pretreatment with either antagonist alone was less effective. These findings suggest that either cocaine o r heroin alone was sufficient to substitute for the cocaine/heroin tra ining combination. To characterize the discriminative stimulus propert ies of this speedball more fully, a series of cocaine-like and heroin- like agonists were studied in substitution tests. The indirect dopamin e agonists CFT, amphetamine and bupropion and the mu opioid agonists a lfentanil, fentanyl and morphine produced high levels of speedball-app ropriate responding. However, the indirect dopamine agonist GBR12909, the D1 dopamine agonist SKF82958, the D2 dopamine agonist quinpirole a nd the partial mu opioid agonist nalbuphine did not substitute for the cocaine/heroin combination. Because these compounds produce discrimin ative stimulus effects similar to either cocaine or mu opioid agonists alone, these findings suggest that the discriminative stimulus effect s of the cocaine/heroin combination do not overlap completely with the effects of cocaine and heroin alone. Finally, a series of compounds t hat produce partial or no substitution for cocaine or mu agonists alon e also did not substitute for the cocaine/heroin combination, which in dicates that the discriminative stimulus effects of the combination we re 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 bo th component drugs.