Diazepam and pentobarbital dependence in the rat

Abstract

Diazepam (100–133 mg/kg/day), administered chronically through a gastric fistula, and pentobarbital (ca 692 mg/kg/day), administered chronically in food, were studied for their dependence producing properties in Sprague-Dawley female rats. The diazepam abstinence syndrome was apparent 10 to 20 hours after withdrawal, persisted for over 60 hours and consisted of poker tail, explosive awakenings, digging in sawdust, jerks, tremors, wet dog shakes, hostility, decreased food and water consumption and weight loss. The pentobarbital abstinence syndrome came on rapidly peaking within 10 hours and was largely over by 16 hours. The pentobarbital abstinence syndrome differed from diazepam's by the presence of grand mal, clonic and atypical convulsions. Diazepam completely and in a dose related way suppressed the diazepam abstinence syndrome. Similarly pentobarbital suppressed the pentobarbital abstinence syndrome. The signs which could be suppressed in a dose related manner were different for the diazepam and pentobarbital abstinence syndromes. Diazepam only partially suppressed the pentobarbital abstinence syndrome and pentobarbital only partially suppressed the diazepam abstinence syndrome. These data indicate that diazepam and pentobarbital produce different types of dependencies in the rat and are not equivalent in suppressing signs of abstinence.