Self-administration of cocaine and heroin combinations by rhesus monkeys responding under a progressive-ratio...

The present study examined the reinforcing effects of cocaine and heroin, alone and combined, in rhesus monkeys (n = 4) responding under a progressive-ratio (PR) schedule. The PR schedule consisted of five components, each made up of four trials (i.e., 20 trials total), with each trial in a component having the same response requirement. The initial response requirement was fixed-ratio (FR) 120, which doubled across components to a maximum of FR1920. A trial ended with an injection or the expiration of a 15-min limited hold and the inter-trial interval was 30 min. Cocaine dose-response functions (13-400 micrograms/kg per injection) for injections/ session were monophasic, i.e., increased with dose until responding reached an asymptote or a peak. Heroin dose-response functions (1.6-100 micrograms/kg per injection) for injections/session were biphasic functions. i.e., increased to a peak and then decreased, whereas heroin dose-response functions for response rate were monophasic and reached an asymptote. When cocaine (1.6-200 micrograms/kg per injection) was combined with heroin (0.4-6.4 micrograms/kg per injection), low doses of cocaine (3.2-25 micrograms/kg per injection) and heroin (0.4-1.6 micrograms/kg per injection) that did not maintain behavior when tested alone did so when tested in combination. Combination with heroin resulted in a leftward shift in the cocaine dose-response functions, indicating that heroin increased the potency of cocaine as a reinforcer. This heroin-induced increase in cocaine's reinforcing potency may be a contributing factor to abuse of cocaine and heroin combinations (i.e., "speedballs") in humans. However, maximum injections/session for cocaine combined with heroin were not different from cocaine alone, suggesting that the reinforcing efficacy of combinations of cocaine and heroin were not higher than that of cocaine alone.