The reinforcing and discriminative stimulus effects of self‐administered cocaine in monkeys: a within‐subject design

Abstract

Drug discrimination (DD) and drug self‐administration (SA) are preclinical assays used to assess abuse liability; however, studies have demonstrated that discriminative stimulus (SD) and reinforcing (SR) effects do not always share a predictive relationship. To date, all preclinical studies with cocaine have examined the SD and SR effects in separate groups of subjects. The use of group‐design studies may partially account for our limited understanding of the relationship between SD and SR effects. To this end, drug naïve rhesus macaques were trained to discriminate self‐administered cocaine from saline under a novel chained‐schedule to evaluate the mechanisms underlying SD effects and reinforcing efficacy using within‐subject analyses. Each subject acquired SA under a progressive‐ratio schedule with no prior SA training. Significant differences in breakpoint between saline and 0.1 mg/kg cocaine were evident by training session 5 in all subjects. DD dose‐effect curves (0.03–0.3 mg/kg) were determined for each subject and compared to SA dose‐effect curves. For each subject, there was at least one cocaine dose that did not engender drug‐appropriate responding during DD yet functioned as a reinforcer during SA, suggesting that SD and SR effects provide dissimilar information. This within‐subject model may provide novel information related to the neuropharmacology of both effects. DA021920, DA06634