Abstract

The method of "maximally tolerable" dosing technique for establishing a reproducible state of barbiturate dependence in cats was used for the study. The development of tolerance in animals treated by this method has been quantitatively assessed. Sodium pentobarbital was administered morning and evening for 35 days via a plastic tube implanted into the stomach through the abdominal wall. A range of neurological signs of intoxication was scored before and after each dose and during the day at certain preset intervals. Based on the scoring of neurological impairment, each cat was given the maximally tolerable anesthetic dose of sodium pentobarbital. All of the animals treated by this method exhibited severe withdrawal signs upon abrupt withdrawal of the drug. For each cat, blood pentobarbital concentrations were determined every day before and 1 to 11/4 hours after the morning dose. Also, a complete blood pentobarbital elimination study was made on days 1, 7, 14, 21, 28 and 35 of the regimen. These results distinguished between dispositional and functional tolerance. The dispositional tolerance developed maximally within a week and was maintained at that level as long as the treatment was continued. The functional tolerance, on the other hand, developed more gradually and progressed with continued treatment.