Increased α2- and β1-adrenoceptor densities in postmortem brain of subjects with depression: Differential effect of antidepressant treatment

Background: Brain alpha(2)- and beta-adrenoceptor alterations have been suggested in suicide and major depressive disorder. Methods: The densities of alpha(2)-, beta(1)- and beta(2)-adrenoceptors in postmortem prefrontal cortex of 26 subjects with depression were compared with those of age-, gender- and postmortem delay-matched controls. The effect of antidepressant treatment on alpha(2)- and beta-adrenoceptor densities was also evaluated, alpha(2)-and beta-adrenoceptor densities were measured by saturation experiments with respective radioligands [H-3] UK14304 and [H-3]CGP12177. beta(1)- and beta(2)-adrenoceptor subtype densities were dissected by means of beta(1)-adrenoceptor selective antagonist CGP20712A. Results: Both, alpha(2)- and beta(1)-adrenoceptors densities were higher in antidepressant-free depressed subjects (n=14) than those in matched controls (Delta similar to 24%, p=0.013 and Delta similar to 20%, p=0.044, respectively). In antidepressant-treated subjects (n=12), alpha(2)-adrenoceptor density remained increased over that in controls (Delta similar to 20%), suggesting a resistance of alpha(2)-adrenoceptors to the down-regulatory effect of antidepressants. By contrast, beta(1)-adrenoceptor density in antidepressant-treated depressed subjects was not different from controls, suggesting a possible down-regulation by antidepressants. The down-regulation of beta(1)-adrenoceptor density in antidepressant-treated depressed subjects differs from the unaltered beta(1)-adrenoceptor density observed in citalopram-treated rats and in a group of non-depressed subjects also treated with antidepressants (n=6). beta(2)-adrenoceptor density was not altered in depressed subjects independently of treatment. Limitations: Antidepressant-treated subjects had been treated with a heterogeneous variety of antidepressant drugs. The results should be understood in the context of suicide victims with depression. Conclusions: These results show the up-regulation of brain alpha(2)- and beta(1)-adrenoceptors in depression and suggest that the regulation induced by chronic antidepressant treatment would be altered in these subjects. (C) 2014 Elsevier B.V. All rights reserved.