Over the last two decades, evidence has been obtained to suggest that beta adrenergic receptors in the brain are involved in the effects of antidepressant drugs. More recently, it has been suggested, based on the results of preclinical and clinical studies, that beta adrenergic agonists possess antidepressant activity. However, these studies have been limited by the lack of availability of beta agonists that penetrate into the brain and act centrally following systemic administration. Recently, it has become apparent that two beta agonists clenbuterol and prenalterol are centrally acting. Thus, it is of interest to begin to assess the behavioral and neuropharmacologic effects of these two agonists. It is also important to identify additional centrally acting beta agonists. The proposed studies, using rats, of clenbuterol and prenalterol will, in a quantitative manner, 1) identify and characterize their effects on behavior, 2) identify and characterize their interactions with beta receptors and their activation of adenylate cyclase in certain brain regions, and 3) begin to assess whether their behavioral effects depend on agonist interaction with the beta receptor-linked adenylate cyclase system in the brain. The identification and testing of additional centrally acting compounds will eventually permit generalization of the results beyond clenbuterol and prenalterol. The results of the proposed studies will provide information on the neuropsychopharmacologic effects of what may be a novel class of antidepressant agents. Furthermore, the results will provide much basic information on the behavioral and neuropharmacologic consequences of stimulation of beta receptors in the brain.
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