Effects of propranolol on barbital dependence formation and withdrawal signs

We studied the involvement of beta-adrenoceptors in the physical dependence formation of barbital. 1. Propranolol (at a dose of 0.5 or 1.0 mg/g food) and barbital were applied simultaneously as a mixture with animal food (barbital-propranolol combination). Barbital was applied on a schedule of gradually increasing dosages from 0.5-and-1.0 to 6-and-8 mg/g food over 36 days. Only the animals dosed with barbital exhibited severe withdrawal signs such as spontaneous withdrawal convulsions. The animals dosed with propranolol alone showed no changes even on withdrawal of the drug. The formation of physical dependence on barbital was obviously inhibited by the combination of barbital and propranolol. 2. Cross-application of propranolol (30 and 60 mg/kg, p.o., and 10 and 30 mg/kg, i.p.) following withdrawal of barbital resulted in the inhibition of the spontaneous withdrawal convulsions, muscle rigidity and hyperirritability. It also inhibited significantly tranylcypromine-induced convulsions, while it failed to inhibit similarly induced hyperthermia. These results including previous findings of effects of monoamine-related compounds on barbital withdrawal convulsions suggest that the balance of activities of noradrenergic neurons, especially that of alpha- and beta- receptors, has great influence on both the formation of physical dependence on barbital and the manifestation of withdrawal convulsions.