Peripheral mediation of effects of clenbuterol on locomotor and investigatory behavior in rats.

Clenbuterol is one of the few beta adrenergic agonists that readily passes the blood-brain barrier. Hence, the behavioral effects in rats of systemic administrations of clenbuterol have been used as a reflection of the activation of central beta receptors. The present experiments were designed to test the hypothesis that the reduction in locomotor activity induced by clenbuterol is mediated by central rather than peripheral beta receptors. First, dose-dependent reductions in ambulation, holepoking, and rearing were established following intraperitoneal injections of 0.004 to 1.0 mg/kg clenbuterol. These effects were then found to be similar to those of 0.4 mg/kg isoproterenol, a mixed beta adrenergic agonist that does not enter the brain after systemic administration. The behaviorally suppressive effects of either 0.4 mg/kg isoproterenol or 0.05 mg/kg clenbuterol were found to be completely antagonized by pretreatment with a 10.0 mg/kg dose of nadolol, a beta antagonist that does not penetrate the brain when administered systemically. Nadolol itself had no significant effects on behavior. These results indicate that these behavioral effects of systemic administrations of clenbuterol are mediated by the activation of peripheral rather than central beta adrenergic receptors.