Effects of nifedipine on physical dependence on barbital or diazepam in rats

The effects of nifedipine on the development of physical dependence on barbital and diazepam in rats were examined using the drug-admixed food method. Rats were chronically treated with either barbital- or barbital in combination with nifedipine-admixed food for 28 days, and with either diazepam- or diazepam in combination with nifedipine-admixed food for 26 days, on schedules of gradually increasing doses of barbital or diazepam. Withdrawal was conducted by substituting normal food for drug-admixed food on the last day of the treatment. Co-administration of nifedipine with barbital potentiated weight loss and withdrawal scores after the termination of barbital treatment. However, the withdrawal signs after the termination of diazepam treatment were not affected by co-administration of nifedipine with diazepam. These results suggest that nifedipine potentiates the development of physical dependence on barbital but not diazepam. It is known that co-administration of dihydropyridine derivative nitrendipine suppresses the development of physical dependence on ethanol. Basing on the differences in sensitivity of central depressants, barbiturates, benzodiazepines and ethanol, to three types of voltage-dependent Ca2+ channels, such as L-, N- and T-types studied so far, the development of physical dependence on central depressants may be modified differently by L-type Ca2+ channel blockers, corresponding to respective depressants.