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

The effects of the opioid antagonist naloxone were studied with three monke ys under a mutually exclusive fixed-interval 15 s (FI 15 s) schedule of rei nforcement. Under this schedule, at the end of each interval, the monkey co uld obtain one liquid delivery from either the spout that delivered methado ne (0.8 mg/ml) or the spout that delivered vehicle (deionized water). Nalox one doses from 0.0125 to 0.2 mg/kg (IM daily 10 min prior to the session) w ere 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 se ssion for two of the three monkeys. At higher doses naloxone decreased meth adone deliveries in all three monkeys. Naloxone's effects were usually grea ter during the descending dose series than during the ascending series. The se findings suggest that a history of naloxone injections is one determinan t of response to the drug. Vehicle maintained responding was generally low and not changed by naloxone in a systematic way. The time course of methado ne deliveries showed that naloxone's effects were greatest in the first hou r of the session and were a direct function of dose. These experiments demo nstrate that oral methadone reinforced behavior is sensitive to naloxone pr etreatment and that the effects of naloxone are a direct function of dose. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.