Repeated treatment with clenbuterol produces desensitization of rat brain beta- and alpha 2-adrenoceptors without changes of alpha 1-adrenoceptors.

Abstract

The effects of single and repeated administrations of the beta-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 beta- (clenbuterol), alpha 2-(clonidine) and alpha 1-(phenylephrine) adrenergic stimulation. Furthermore, the effects of such treatment on beta- and beta 1-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 beta-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 beta-agonist produces a rapid appearance of beta- and alpha 2-adrenoceptor subsensitivity, which it not followed by alpha 1-adrenoceptor changes.