Abstract
Phenobarbital, chordiazepoxide, diazepam and/or morphine were repeatedly administered to both male and female rats (N=10) for 4 ?? 6 weeks. The drug dose was gradully increased from 5 to 10, 20, 40, 80 and 160 mg/kg once daily (p.o.) at seven day intervals. In the case of morphine, the last dose was 40 mg/kg. The drugs were constantly withdrawn for 24 hr at 8 day intervals. None of the rats were given drugs for 16 days after administration of the last scheduled dose in order to recover their initial weight (Exp. I). Onset of dependence formation, decrease in body weight and food intake, days required to reach the maximum decrease in body weight and duration of withdrawal signs were observed throughout this experiment. The rats (drug dependence-experienced rats) who survived the first stage of this experiment were continuously subjected to re-administration by the same dasage schedule as in Exp. I (seven days of drug administration, 48 hr of withdrawal). The re-administered rats showed a more rapid onset of dependence formation and a longer duration of decrease in body weight during 16 days withdrawal than did the naive rats. It is concluded, that in addition to the decrease in body weight by withdrawal plus duration of the withdrawal signs, the onset of drug dependence formation is also a specific factor.
