Orally delivered methadone as a reinforcer: Effects of the opioid antagonist naloxone.

The effects of the opioid antagonist naloxone were studied with three monkeys under a mutually exclusive fixed-interval 15 s (FI 15 s) schedule of reinforcement. Under this schedule, at the end of each interval, the monkey could obtain one liquid delivery from either the spout that delivered methadone (0.8 mg/ml) or the spout that delivered vehicle (deionized water). Naloxone doses from 0.0125 to 0.2 mg/kg (IM daily 10 min prior to the session) were studied in an ascending then descending order. In the ascending series, low naloxone doses produced increases of methadone deliveries in the first hour of the session for three monkeys and increases over the entire 3-h session for two of the three monkeys. At higher doses naloxone decreased methadone deliveries in all three monkeys. Naloxone's effects were usually greater during the descending dose series than during the ascending series. These findings suggest that a history of naloxone injections is one determinant of response to the drug. Vehicle maintained responding was generally low and not changed by naloxone in a systematic way. The time course of methadone deliveries showed that naloxone's effects were greatest in the first hour of the session and were a direct function of dose. These experiments demonstrate that oral methadone reinforced behavior is sensitive to naloxone pretreatment and that the effects of naloxone are a direct function of dose.