Orally delivered methadone as a reinforcer for rhesus monkeys: The relationship between drug concentration and choice

The relative reinforcing effects of orally delivered methadone were studied in five male rhesus monkeys. Drug deliveries were available under either a fixed-ratio (FR) or a fixed-interval (FI) schedule. Three concentrations of methadone, low (0.05 mg/ml), intermediate (0.2 mg/ml), and high (0.8 mg/ml) were delivered in 0.65 ml volumes. In the first experiment, monkeys were presented with a choice paradigm. Under independent FR schedules responding led to a delivery of either a methadone solution or the water vehicle. For each concentration, deliveries of a methadone solution maintained higher response rates than did deliveries of water. In the second experiment, methadone concentrations were tested in pairs in the following sequence: high vs. low, high vs. intermediate, intermediate vs. low, high vs. intermediate (retest), and high vs. low (retest). The retest of the last two pairs was designed to counterbalance the test sequence, so that order effects, if they existed, could be detected. Regardless of the schedule, the higher concentration of the methadone pair maintained a greater response rate than did the lower concentration. The present results are consistent with the generalization based on other studies that over a broad range of concentrations and across pharmacological classes, reinforcement schedules, and routes of administration, reinforcing effects increase with increases in drug concentration.