Induction of physical dependence on pentobarbital by new infusion method in the rat

1. A new intermittent intravenous infusion method was developed for the induction of tolerance to and physical dependence on pentobarbital in rats. 2. Female and male rats were injected with pentobarbital (20 mg/kg/injection) through an implanted intravenous cannula. 3. The rats were allowed to receive an injection after the completion of a fixed amount of behavioral activity counted from the preceding injection, and therefore, the sedative and hypnotic effects of pentobarbital were used as an index in the determination of the injection intervals. 4. During pentobarbital treatment, the number of pentobarbital injections per day rapidly increased and stabilized (approximately 40: male, approximately 30: female) on the third to fifth day. 5. Upon withdrawal, the female and male rats who were maintained on pentobarbital administration of more than 30 and 40 injections/day for approximately 10 days manifested withdrawal signs which included spontaneous convulsion. 6. These results suggest that a new infusion method exists to produce a high degree of physical dependence in rats on a short-acting barbiturates, pentobarbital.