Methadone dependence in the rat.

Physical dependence on methadone was induced in rats by an initial "forced drinking" procedure and subsequently by i.p. administration of the drug. In a subsequent Experimental Phase of the study the physical dependence of one group was sustained by a "methadone maintenance" treatment, while two other groups were withdrawn from the drug, one gradually and one abruptly. When relapse trials were carried out during a Readdiction Phase it was found that the maintained group voluntarily consumed significantly greater amounts of methadone than did the two withdrawal groups. These groups did not differ between themselves but did in turn ingest significantly more methadone than a control group with no prior exposure to the drug. The characteristic loss of body weight reliably found during withdrawal from morphine was not demonstrated. This may have been due to the unexpected weight loss which occurred during the last stage of the initial Addiction Phase. The dependent variables of amount of methadone solution and the percentage of fluid consumed as methadone solution correlated highly. However the amount of methadone solution ingested was a better indicator of addiction liability as it was not influenced by fluctuations in the amount of water consumed by the animals.