Physical dependence produced by long duration, low dose chronic barbital treatment

Barbiturate physical dependence was produced by twice-daily administration of Na barbital to cats according to the "low" dose barbiturate protocol (Okamoto et al., J. Pharmacol. Exp. Ther. 207: 906, 1978). The duration of treatment was 1, 2, 3, 5, 9 or 14 weeks. Pharmacodynamic tolerance was assessed by relating the degree of neurofunctional impairment to the blood barbital concentration at the time when the functional test was performed. Evaluation of withdrawal was based on whole-animal observation and subjective assessment of overt withdrawal signs. Motor activity and withdrawal convulsions were monitored continuously by an activity recording device. It was found that the pharmacodynamic tolerance and physical dependence continued to develop throughout the treatment period and no apparent ceiling on these phenomena was observed. The "low" level chronic dosing merely prolonged the time required to develop physical dependence of severity comparable to that produced by shorter durations of "high" level chronic dosing.