Tolerance to effects of cocaine on behavior under a response-initiated fixed-interval schedule.

Tolerance to effects of cocaine can be modulated by schedules of reinforcement. With multiple ratio schedules, research has shown an inverse relationship between ratio requirement and amount of tolerance that resulted from daily administration of the drug. In contrast, tolerance to the effects of cocaine on behavior under multiple interval schedules generally has developed regardless of interval value. Under interval schedules reinforcement depends on the animal making one response following a time interval. Thus, as time to respond increases, the time to reinforcement decreases. On the other hand, fixed ratio schedules require a specified number of responses to be made prior to reinforcement. Therefore, delaying the initiation of responding does not coincide with a significant decrease in the time to reinforcement. In the current experiment, 6 pigeons were trained to respond under a three-component multiple schedule, with a different tandem fixed-ratio 1 fixed-interval schedule in each component. The multiple schedule required one response, which was followed by one of three fixed-interval values (5, 15, or 60 s). Thus, the multiple schedule was interval-like because after the fixed-ratio 1, only one more response was required for reinforcement, but it was also ratio-like because the length of the pause at the beginning of each interreinforcer interval affected the time until the next reinforcer. Acute administration of cocaine generally resulted in dose-dependent decreases in responding. Chronic (i.e., daily) administration of a rate-decreasing dose resulted in tolerance patterns similar to those usually obtained with multiple ratio schedules. That is, the magnitude of tolerance was related inversely to schedule size. These results suggest that delay to reinforcement from the initial response may play a role in the development of schedule-parameter-related tolerance.