Role of catecholamines in the development of tolerance to barbiturates and ethanol

The destruction of noradrenergic systems in brain by administration of 6-hydroxydopamine prior to chronic ethanol treatment prevented the development of tolerance to ethanol. Animals pretreated with 6-hydroxy dopamine also showed no cross tolerance to barbiturates. Destruction of noradrenergic systems prior to chronic treatment with barbiturates also partially prevented the development of tolerance to pentobarbital. 6-Hydroxydopamine pretreatment had little effect on the signs of physical dependence produced by ethanol. The possible dissociation of tolerance and dependence and the role of noradrenergic systems in these phenomena is discussed.