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 assess if PR responding using cocaine reinforcement in rats would: a) be acquired rapidly; b) be maintained on a stable baseline for long periods; and c) provide data on the effect of changing the dose of cocaine that are amenable to statistical analysis. In addition, the effects of pretreatments with SCH23390, a D1 receptor antagonist, or ondansetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were tested against several doses of cocaine. Stable performance of PR cocaine self-administration (0.90 mg/kg) was acquired within 10 training sessions and was maintained for over 50 training sessions. Increasing the dose of cocaine 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 (ISRT: time between each cocaine infusion). In terms of statistical analysis, the number of reinforcers obtained was found to be preferable to the highest ratio completed as a measure of breakpoint. Pretreatment with SCH23390 significantly reduced the breakpoint; this reduction was not due to a motor-incapacitating effect of SCH23390 because the ISRT showed a tendency to be shortened by SCH23390. Pretreatment with ondansetron failed to significantly affect either the number of reinforcers obtained or the ISRT. These results show that rats can readily acquire the task of self-administration of cocaine under a PR schedule and maintain a stable baseline for an extended period. Further, a PR schedule appears to be suitable for the study of pharmacological treatments that might affect cocaine self-administration. Simultaneous monitoring of the breakpoint and of the ISRT determines if a decrease in the breakpoint is the result of a motor-incapacitating side effect of the pretreatment.
Depoortere
R Y
RY
Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107-2699.
Li
D H
DH
Lane
J D
JD
Emmett-Oglesby
M W
MW
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012055:Reinforcement Schedule; D012646:Self Administration
D001552:Benzazepines; D017448:Receptors, Dopamine D2; D017294:Ondansetron; D003042:Cocaine