PARAMETERS OF SELF-ADMINISTRATION OF COCAINE IN RATS UNDER A PROGRESSIVE-RATIO SCHEDULE

Progressive-ratio (PR) schedules may provide a more direct measure of drug-reinforcing efficacy than the more traditionally used fixed-ratio schedules. Under a PR schedule, an increasing number of lever presses is required for the delivery of each successive reinforcer. However, there have been few studies of fundamental parameters of cocaine self- administration under a PR schedule. This study was undertaken to asses s if PR responding using cocaine reinforcement in rats would: a) be ac quired rapidly; b) be maintained on a stable baseline for long periods ; and c) provide data on the effect of changing the dose of cocaine th at are amenable to statistical analysis. In addition, the effects of p retreatments with SCH23390, a D1 receptor antagonist, or ondansetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were tested agains t several doses of cocaine. Stable performance of PR cocaine self-admi nistration (0.90 mg/kg) was acquired within 10 training sessions and w as maintained for over 50 training sessions. Increasing the dose of co caine from 0.10-2.70 mg/kg resulted in a directly related increase in a) the number of reinforcers obtained, b) the highest ratio completed, and c) the interreinforcer time (IS(R)T: time between each cocaine in fusion). In terms of statistical analysis, the number of reinforcers o btained was found to be preferable to the highest ratio completed as a measure of breakpoint. Pretreatment with SCH23390 significantly reduc ed the breakpoint; this reduction was not due to a motor-incapacitatin g effect of SCH23390 because the IS(R)T showed a tendency to be shorte ned by SCH23390. Pretreatment with ondansetron failed to significantly affect either the number of reinforcers obtained or the IS(R)T. These results show that rats can readily acquire the task of self-administr ation of cocaine under a PR schedule and maintain a stable baseline fo r an extended period. Further, a PR schedule appears to be suitable fo r the study of pharmacological treatments that might affect cocaine se lf-administration. Simultaneous monitoring of the breakpoint and of th e IS(R)T determines if a decrease in the breakpoint is the result of a motor-incapacitating side effect of the pretreatment.