ORALLY DELIVERED METHADONE AS A REINFORCER IN RHESUS-MONKEYS

Methadone usually is taken orally for drug abuse treatment in humans b ut oral methadone self-administration by laboratory animals has not be en investigated extensively. The present study examines acquisition an d maintenance of oral methadone maintained responding in four adult ma le rhesus monkeys. Drug solution was available from one liquid deliver y system and water from a second system during daily 3-h sessions. Loc ations of liquids were reversed each session, and liquid (0.65 mi per delivery) was delivered according to a fixed-ratio reinforcement sched ule. Initially a test for the reinforcing effects of 0.00625-0.4 mg/ml methadone solutions was carried out but a consistent preference for d rug over water was not seen. To establish methadone as a reinforcer, a fading procedure was used in which responding was first maintained by solutions of methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0 325-2.0% w/v). Subsequently, the concentration of the ethanol in the c ombination was gradually reduced to zero. Methadone-maintained respond ing (0.4 mg/ml) persisted when ethanol was no longer present. To confi rm that the drug was serving as a reinforcer, the dose was varied: (a) by changing the volume delivered while the concentration was held con stant and (b) by changing the concentration of the methadone while the volume per delivery was held constant. Over a wide range of doses, de liveries of methadone solution usually exceeded deliveries of concurre ntly available water. Orderly relationships were observed among methad one dose, response rate, and drug intake. The study of oral self-admin istration of opioid drugs by nonhuman primates may be a useful strateg y development and evaluation of new drug substitution or replacement t herapies.