Abstract
Utilizing a drug-admixed diet, rats were made physically dependent on morphine, codeine and phenobarbital in one week, on meprobamate in two weeks and these same rats were used for the two days substitution test and the time course of body weight during each drug withdrawal. In the substitution test, codeine-admixed food could be substituted for morphine-admixed food and the drug dependence still maintained. The reverse was also possible. Meprobamate-admixed food could not be substituted for phenobarbital-admixed food, however, the reverse was possible. Drug dependence could be maintained. Body weight of morphine and codeine dependent rats suddenly decreased following morphine and codeine withdrawal. The body weight loss reached a maximum after approx. 38 hr and 46 hr respectively, but suddenly increased when reverting back to the drug-admixed food. Body weight of phenobarbital dependent rats increased for 10 hr following provision of the drug-admixed diet. It is concluded that a drug-admixed diet is a useful tool for screening physical dependence liability of new preparations.
