RELATIONSHIP BETWEEN THE DISCRIMINATIVE STIMULUS EFFECTS AND PLASMA-CONCENTRATIONS OF INTRAMUSCULAR COCAINE IN RHESUS-MONKEYS

The relationship between the discriminative stimulus effects and plasm a pharmacokinetics of cocaine was evaluated in six rhesus monkeys trai ned to discriminate cocaine (0.4 mg/kg, IM) from saline under a FR30 s chedule of food presentation. The same monkeys were tested in two proc edures. In a cumulative dosing procedure, five cumulative doses of coc aine (0.013-1.3 mg/kg) were administered and discriminative stimulus e ffects were evaluated IO min after the administration of each dose. Co caine plasma concentrations were measured in separate sessions using t he same doses and interdose intervals. In a single dosing procedure, t he time-courses of the discriminative stimulus effects and plasma conc entrations of cocaine were assessed after the administration of cocain e (0.4 mg/kg). A close correspondence between cocaine's discriminative stimulus effects and plasma concentrations was obtained in both proce dures. Cocaine was virtually undetectable in plasma at doses that prod uced saline-appropriate responding (0.013 and 0.04 mg/kg), whereas inc reasing plasma concentrations were measured at doses that produced pri marily cocaine-appropriate responding (0.13 mg/kg or higher). The time -course of the discriminative stimulus effects of cocaine was characte rized by a rapid onset (within 1-3 min post-cocaine) and offset (withi n 20-60 min post-cocaine). Peak plasma levels were obtained at 10 min post-cocaine. No differences in plasma concentrations were found 10 mi n after the administration of a cumulative versus a single dose of coc aine 0.4 mg/kg (mean, 75.8 and 74.0 ng/ml, respectively). Cocaine plas ma concentrations lasted longer than its discriminative stimulus effec ts. The results of the present study confirm that the cumulative dosin g procedure used yields plasma concentrations of cocaine that are simi lar to the concentrations obtained after single cocaine dosing.