Recent findings demonstrate that orally delivered methadone can serve as a reinforcer for rhesus monkeys. There are important parallels with methadone maintenance patients in that the drug is taken orally and functions as a reinforcer. In laboratory studies with methadone maintenance patients, delivery of small volumes of methadone maintains responding under fixed-ratios and at much higher rates than the concurrently available vehicle. These findings are the same as those obtained with monkeys for who orally delivered methadone serves as a reinforcer. If monkeys are simply given the option of drinking a methadone solution or water, they will avoid the methadone solution. Thus a training procedure is necessary. A fading procedure can be used to establish the drug as a reinforcer. Across blocks of sessions increasing amounts of methadone are added to a 2% ethanol solution until a concentration of 0.4 mg/ml is reached. Subsequently, across blocks of sessions the ethanol concentration is gradually decreased to zero: Methadone drinking persists, and the monkeys consume much larger volumes of the drug solution than of the concurrently available water vehicle. Moreover, the positions of the drug and vehicle liquids are reversed each day, and the monkeys consistently """"""""track"""""""" the drug solution. The proposed research will examine a number of variables that are of importance in controlling drug reinforced behavior. These include drug dose, schedule size, food restriction, abused drug combinations, competing reinforcers, and antagonist effects. The relative reinforcing effects of different drug doses will be determined, and interactions among some of the variables will be studied. These studies will permit an initial characterization of oral opioid reinforced behavior in a nonhuman primate, and the results will provide an empirical foundation for future studies. One outcome will be a chronic stable laboratory preparation that will be useful in studies that have either a basic science or clinical basis. In particular this preparation will be useful in medication development. It will be possible to carry out long-term sequential studies of drugs that alter opioid reinforced behavior.
| Wang, N S; Brown, V L; Grabowski, J et al. (2001) Reinforcement by orally delivered methadone, cocaine, and methadone-cocaine combinations in rhesus monkeys: are the combinations better reinforcers? Psychopharmacology (Berl) 156:63-72 |
| Meisch, R A (2000) Relative persistence of behavior: a fundamental measure of relative reinforcing effects. Exp Clin Psychopharmacol 8:333-49 |
| Wang, N S; Stewart, R B; Meisch, R A (1999) Orally delivered methadone as a reinforcer: Effects of the opioid antagonist naloxone. Drug Alcohol Depend 55:79-84 |
| Meisch, R A; Stewart, R B; Wang, N S (1996) Orally delivered methadone as a reinforcer for rhesus monkeys: the relationship between drug concentration and choice. Pharmacol Biochem Behav 54:547-54 |
| Stewart, R B; Grabowski, J; Wang, N S et al. (1996) Orally delivered methadone as a reinforcer in rhesus monkeys. Psychopharmacology (Berl) 123:111-8 |
