Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

Abstract

Rhesus monkeys (n=5) were prepared with chronic IV catheters and trained to lever press under a PR schedule of drug injection. The schedule consisted of five components, each made up of four trials (i.e., 20 trials total). Each trial within a component had the same response requirement. The response requirement in the first component was 120/trial and doubled in successive components to a maximum of 1920 in the fifth. A trial ended with an injection or the expiration of a 12-min limited hold (LH). The inter-trial interval (ITI) was 15 or 30 min. Following an injection or expiration of the LH, all stimulus lights were extinguished and responding had no consequence for the remainder of the trial. A session ended when either all 20 injections were self-administered or the response requirement was not met within the LH for two consecutive trials. The number of injections/session and responses/session increased with dose for cocaine (0.012–0.1 mg/kg per injection) and procaine (0.12–2.0 mg/kg per injection) at both ITI values. At the 15-min ITI, responding decreased again at higher doses in some monkeys with cocaine and in all monkeys with procaine. At maximum, cocaine maintained significantly more injections and responses/session when the ITI was 30 min than when it was 15 min. In contrast, the increase in ITI did not increase the maximum maintained by procaine. Cocaine was approximately 10-fold more potent than procaine and maintained at maximum significantly more injections and responses than procaine when the ITI was 30 min but not when the ITI was 15 min. These results are consistent with previous studies demonstrating that cocaine is a more efficacious positive reinforcer than procaine. Moreover, they extend recent findings suggesting that number of injections/session provides a measure of PR performance that is amenable to statistical analysis and may, therefore, be useful in establishing reliable differences among drugs in terms of relative reinforcing efficacy. Reliable quantification of between-drug differences in reinforcing efficacy can enhance not only estimates of relative abuse liability but also pharmacological analysis of central mechanisms mediating reinforcing effects.