Barbiturate dependence in mice: effects of continuous vs. discontinuous drug administration.

Three groups of DBA/2J mice were continuously exposed for 3, 6 or 9 days to a milled diet containing phenobarbital. Two additional groups were given a discontinuous drug administration schedule with either one or two 24 h drug-free periods interpolated among the 6 or 9 days of phenobarbital consumption, respectively. The discontinuous schedule of drug administration significantly attenuated the development of physical dependence as determined by the severity of withdrawal symptoms. Functional tolerance development was also attenuated in a manner that closely paralleled the effects on physical dependence development. The 5 group means showed a perfect rank order correlation between functional tolerance and physical dependence development.