Dependence on phenobarbital but not pentobarbital using drug-adulterated food

Abstract

A drug-adulterated food (DAF) method was used in an attempt to establish physical dependence on either pentobarbital or phenobarbital in male CF1 mice. The mice were acclimated to the control diet for four days and then assigned to treatment groups. Group I continued to receive the control diet; Group II received pentobarbital, 5 mg/g food, increased by 5 mg, daily, for 14 days; Group III received pentobarbital, 5 mg/g food, increased by 5 mg, daily, for 7 days; Group IV received pentobarbital, 10 mg/g food, increased by 10 mg, daily, for 7 days; Group V received phenobarbital at 2.5 mg/g food for 5 days and then 3.0 mg/g food for 2 days. During drug administration, all mice were monitored daily for signs of intoxication, change in body weight, and food consumption. At the end of the drug exposure period all mice received control diet and were observed for signs of withdrawal. Mice in Group II and Group IV demonstrated significant declines in body weight and food consumption and an apparent increase in the degree of intoxication but no signs of withdrawal. Group II mice demonstrated little sign of impairment during exposure to pentobarbital and no withdrawal syndrome was observed. Mice presented phenobarbital were found to exhibit a significant degree of intoxication and a withdrawal syndrome was demonstrated. The data suggest, with respect to the drug administration schedules used, that the DAF method was not suitable for the establishment of physical dependence on pentobarbital in mice.