Independent regulation of β1‐ and β2‐adrenoceptors

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Abstract
1 The down-regulation of β-adrenoceptors has been postulated as a biochemical marker of antidepressant efficacy. Here we demonstrate that chronic treatment with desipramine down-regulates β1-adrenoceptors in rat cerebral cortex and that β-adrenoceptor subtypes can be independently regulated by treatment with different β-adrenoceptor agonists. 2 Desipramine, (±)-clenbuterol, prenalterol, corwin (20 mg kg−1 daily) and corwin (10 mg kg−1 daily) were administered to male, Sprague-Dawley rats, over eight days, by means of osmotic Alzet pumps placed subcutaneously and removed 24 h before analysis. Control rats received vehicle only. The β1- and β2-adrenoceptor populations were measured in cerebral cortex by a modified (–)-[125I]-pindolol receptor binding assay. 3 The conventional antidepressant, desipramine, preferentially down-regulated β1-adrenoceptors whereas the non-selective β-adrenoceptor agonist (±)-clenbuterol preferentially down-regulated β2-adrenoceptors. The β1-selective partial agonist, prenalterol, up-regulated β1-adrenoceptors perhaps acting more as an antagonist than as an agonist. Finally, neither dose of corwin had any significant effect on β-adrenoceptor number.