Pharmacological characterization of the discriminative stimulus effects of clenbuterol in rats

The beta-2 selective adrenergic agonist clenbuterol produces discriminative stimulus effects in rats. Administration of beta adrenergic agonists that do not cross the blood-brain barrier well following peripheral administration either failed to substitute for clenbuterol or resulted in chance levels of drug-appropriate responding; this suggested central mediation of the effects of clenbuterol. This interpretation was supported by the finding that the centrally acting beta adrenergic antagonist propranolol antagonized the discriminative stimulus effects of clenbuterol more potently than did CGP-12177, a hydrophilic beta adrenergic antagonist that has been shown to have very limited central activity. Antagonism experiments using subtype-selective antagonists showed that the beta-2 selective antagonist ICI 118,551 more potently antagonized the discriminative effects of the training dose of clenbuterol than did the beta-1 selective antagonist betaxolol. The present results indicate that the discriminative stimulus effects of clenbuterol provide an in vivo index of activation of central beta-2 adrenergic receptors.