Relative reinforcing effects of different doses of orally delivered cocaine

The relative reinforcing effects of different doses of oral cocaine were investigated in two adult male rhesus monkeys. In the first experiment, a range of cocaine doses (0.1-0.8 mg/ml) was studied with drug and water concurrently available for 3 h each day under identical and independent fixed-ratio schedules. The side positions of the drug and vehicle were alternated from session to session. Drug deliveries always exceeded vehicle deliveries, i.e., orally delivered cocaine functioned as a reinforcer. The highest rates of responding occurred at either the lowest or next to lowest dose (0.1 or 0.2 mg/ml). In the second experiment, pairs of different cocaine doses were systematically presented under identical and independent fixed-ratio schedules. The higher of two concurrently available doses usually maintained the higher response rate. These findings suggest that the relative reinforcing effects of orally delivered cocaine increase with dose. Absolute response rates obtained with single cocaine doses and water concurrently available do not always reflect the magnitude of the reinforcing effects indicated when pairs of cocaine doses are studied together. The results of this study are in agreement with earlier investigations in which the relative reinforcing effects of pairs of intravenous cocaine doses or oral pentobarbital doses were studied. Taken together these findings indicate that, over a range of doses and across pharmacological classes and routes of administration, relative reinforcing effects of a drug increase directly as a function of increases in dose.