Studies on the development of physical dependence on barbitone in the rat and rat atrium.

The mechanisms underlying the development of barbitone dependence have been studied in the rat and in atrial preparations removed from dependent animals. Long-term oral administration to the rat of barbitone, alone or together with the analeptics bemegride or pentylenetetrazol, has shown that the intensity of the withdrawal syndrome generally parallels the degree of associated CNS depression. In addition, the overall relationship between the spontaneous or evoked (chemical or audiogenic) responses of representative drug-withdrawn rats and the inotropic responses of corresponding withdrawn atria to supramaximal nerve stimulation, noradrenaline or Ca2+ was reasonably good. It is proposed that the rat atrial preparation may provide a suitable model system for the study of barbitone dependence in the rat, especially in relation to Ca2+-dependent mechanisms, and that selective calcium antagonists may prove helpful in the management of barbiturate and similar types of drug dependence. The barbitone withdrawal syndrome has been described in terms of a membrane phase distribution hypothesis of drug action.