Reinforcing effects of a combination of ethanol and methadone relative to each drug alone

Studies report a high incidence of alcohol abuse in methadone maintenance patients. There is, however, little data on the reinforcing effects of combinations of ethanol and methadone. In the present study, oral self-administration of a combination of 1% (w/v) ethanol and 0.2 mg/ml methadone was compared to each drug alone in three rhesus monkeys in which methadone alone was not a reinforcer. In Experiment 1, ethanol and the combination, but not methadone alone, served as reinforcers. In Experiment 2, there was no preference for ethanol or the combination at fixed ratio (FR) 8 or 16. When the FR size was doubled (FR 16 or 32), all three animals preferred the combination to 1% ethanol. Experiment 3 further examined the effect of work requirement on preference for ethanol or the combination by varying FR values [1, 2, 4, 8, 16, or 32]. At lower FRs, ethanol was significantly preferred to the combination. As FR was increased, there was a significant reduction in preference for ethanol over the combination. The results show that an ethanol + methadone combination will be orally self-administered by monkeys and suggest that work requirement differentially modifies preference for the combination and ethanol alone.