A comparison of the neurochemical and behavioral effects of clenbuterol and desipramine.
Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS beta-adrenoceptors and attenuate brain adenylate cyclase activity, beta-adrenoceptor agonists may also possess antidepressant properties. We compared the effects of the centrally acting beta-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 beta-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 beta-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 beta-receptors induced by clenbuterol (10 mg/kg per day). Propranolol (5 mg/kg per day) alone up-regulated frontal cortex beta-adrenoceptors, but had no significant effect on swimming performance. These data suggest that the physiological consequences of beta-adrenoceptor 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.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002976:Clenbuterol / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013550:Swimming
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D003891:Desipramine; D002976:Clenbuterol