Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS β-adrenoceptors and attenuate brain adenylate cyclase activity, β- adrenoceptor agonist may also possess antidepressant properties. We compared the effects of the centrally acting β-adrenoceptor agonist clenbuterol (5, 10 and 35 mg/kg per day), and the combination of propranolol (5 mg/kg per day) and clenbuterol (10 mg/kg per day), with desipramine (15 mg/kg per day) on forced swim test performance and on cortical β-adrenoceptors in rats following 7 days of drug administration. Desipramine (15 mg/kg per day), and clenbuterol (10 and 35 mg/kg per day, but not 5 mg/kg per day) both significantly reduced immobility in the forced swim test. Frontal cortex β-adrenoceptors were significantly down-regulated after desipramine and all 3 doses of clenbuterol. The co-administration of propranolol (5 mg/kg per day) blocked both the reduction in immobility and down-regulation of cortical β-adrenoceptors induced by clenbuterol (10 mg/kg per day). Propranolol (5 mg/kg per day) alone up-regulated frontal cortex β-adrenoceptors, but had no significant effect on swimming performance. These data suggest that the physiological consequences of β-adrenoceptors down-regulation are important in the mechanism of action of antidepressants. The results also suggest that clenbuterol may be useful in the treatment of depression.
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