Dependence studies of new compounds in the rhesus monkey, rat, and mouse (1985).

Substitution-for-Morphine (SDS) Test. Male and female rhesus monkeys (M. mulatta) weighing 2.5-7.5 kg were used, and they received 3 mg/kg, s.c., of morphine.SO4 every 6 hr. All the animals had received morphine for at least 3 months and were maximally dependent on morphine (Seevers and Deneau 1963). A minimal 2-week recuperation period was allowed between tests. At least 3 monkeys/dose were used. The assay (Aceto and coworkers, 1977 and 1978) was initiated by a subcutaneous injection of the test drug or control substances (morphine and vehicle) into animals in a group that had not received morphine for 14-15 hr and showed definite signs of withdrawal. Each animal was randomly chosen to receive one of the following treatments: a) a dose of the compound under investigation; b) morphine control, 3.0 mg/kg; and c) vehicle control, 1 ml/kg. The animals were scored for suppression of withdrawal signs during a 2.5-hr observation period. The observer was "blind" regarding the choice of treatments. At the end of the study, the data were grouped according to dose and drug. The mean cumulative score ± SEM was calculated and the data illustrated in figure form. If indicated, the data were analyzed using the Kruskal-Wallis ANOVA and post hoc Mann-Whitney U-Tests.