EFFECTS OF EXPOSURE REGIMEN ON CHANGES IN SENSITIVITY TO THE EFFECTS OF COCAINE ON SCHEDULE-CONTROLLED BEHAVIOR IN RHESUS-MONKEYS

It has been reported that conditions of drug exposure can influence ch anges in sensitivity to cocaine upon repeated administration. In the p resent experiment, the behavioral effects of prolonged exposure to con tinuous or intermittent infusion of cocaine were compared in rhesus mo nkeys responding under a multiple component fixed-ratio (FR) schedule of food presentation. In order to quantify changes in sensitivity to c ocaine, cumulative dose-response functions for acute cocaine were dete rmined using a multiple schedule comprised of six 10-minute components separated by time-out periods of 3 minutes. Initially, cocaine decrea sed responding in a dose-related manner. Continuous infusion of cocain e (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., toler ance developed. In contrast, when the same daily dose of cocaine was i njected intermittently (1.0 mg/kg per injection) four times/day to dif ferent monkeys, there was no change in the effects of cocaine on respo nding. The present results support the notion that the dosing regimen is an important determinant of changes in sensitivity to the behaviora l effects of cocaine. Additionally, since sensitization failed to deve lop upon intermittent administration of cocaine, behavioral baseline m ay play a role in changes in sensitivity to cocaine.