Effects of exposure regimen on changes in sensitivity to the effects of cocaine on schedule-controlled behavior in rhesus monkeys

Abstract

It has been reported that conditions of drug exposure can influence changes in sensitivity to cocaine upon repeated administration. In the present experiment, the behavioral effects of prolonged exposure to continuous or intermittent infusion of cocaine were compared in rhesus monkeys responding under a multiple component fixed-ratio (FR) schedule of food presentation. In order to quantify changes in sensitivity to cocaine, cumulative dose-response functions for acute cocaine were determined using a multiple schedule comprised of six 10-minute components separated by time-out periods of 3 minutes. Initially, cocaine decreased responding in a dose-related manner. Continuous infusion of cocaine (4 mg/kg per day) for a period of 4 weeks resulted in a 2- to 4-fold shift to the right in the cocaine dose-response function, i.e., tolerance developed. In contrast, when the same daily dose of cocaine was injected intermittently (1.0 mg/kg per injection) four times/day to different monkeys, there was no change in the effects of cocaine on responding. The present results support the notion that the dosing regimen is an important determinant of changes in sensitivity to the behavioral effects of cocaine. Additionally, since sensitization failed to develop upon intermittent administration of cocaine, behavioral baseline may play a role in changes in sensitivity to cocaine.