Repeated treatment with clenbuterol produces desensitization of rat brain β- and α2-adrenoceptors without changes of α 1-adrenoceptors

Abstract

The effects of single and repeated administrations of the β-agonist, clenbuterol (0.5 mg/kg i.p., twice daily for 4 or 7 days) were measured in the open-field test as responsiveness of rats to β- (clenbuterol), α 2- (clonidine) and α 1- (phenylephrine) adrenergic stimulation. Furthermore, the effects of such treatment on β- and β-adrenoceptor binding in the rat brain cortex were studied. Repeated administration of clenbuterol failed to change the exploratory activity, in contrast to the acute sedative effect. Repeated treatment with clenbuterol resulted in a decrease in [ 3H]dihydroalprenolol binding to cortical β-adrenoceptors. A single dose of clenbuterol reduced the clonidine-induced sedation and repeated treatment of clenbuterol abolished this sedation. Clenbuterol did not affect the action of phenylephrine nor did it change the binding of [ 3H]prazosin. These results indicate that repeated administration of a β-agonist produces a rapid appearance of β- and α-adrenoceptor subsensitivity, which it not followed by α 1-adrenoceptor changes.