Does a single priming injection of clenbuterol alter behavioral response to beta-adrenoceptor agonists and...

The present study investigated the extent to which a single priming injection of clenbuterol, a beta-adrenoceptor agonist, could alter the behavioral response (locomotor activity recorded for 30 min with photocell counters) of mice to the subsequent administration of beta-adrenoceptor agonists or antagonists. In mice pretreated with clenbuterol (0.25 mg/kg), the dose-response curve of clenbuterol (0.06 to 2 mg/kg) for reducing locomotor activity was shifted to the right with minimal alteration of the maximal response. The magnitude of the shift was dependent on both the priming dose of clenbuterol and the time interval between the priming and the test injections (maximum between 15 to 24 h, disappearance for intervals exceeding 72 h). The coadministration of propranolol (0.5; 2; 8 mg/kg) dose dependently antagonized the effects of the priming injection of clenbuterol. A previous injection of clenbuterol was also found to reduce the ability of another beta-adrenoceptor stimulant, salbutamol (8 mg/kg), but not apomorphine, to reduce locomotor activity. Finally, previous beta-adrenoceptor stimulation resulted in an enhanced ability of two beta-adrenoceptor antagonists, propranolol (0.125 to 8 mg/kg) and penbutolol (0.5 to 32 mg/kg), to reduce locomotor activity in mice. All these data add to the evidence concerning the remarkable plasticity of central beta-adrenoceptors and indicate that initial stimulation of a class of beta-adrenoceptors may trigger a relatively important, time-dependent alteration in the behavioral reactivity to beta-adrenoceptor agonists and antagonists.