Glucocorticoid treatment increases density of serotonin 5-HT2A receptors in humans.

Background: Interactions between the serotonergic system and the hypothalamic-pituitary-adrenal axis have been suggested, albeit the details for such interactions have yet to be established. Animal studies have shown that the density of serotonin 5-HT2(A) receptors is increased after administration of exogenous glucocorticoids. Objective: The objective of this study was to explore possible changes in the pattern of density and affinity of 5-HT2(A) receptors in humans after treatment with glucocorticoids. Methods: Using a radioactive binding assay, the density and affinity (measured as B-max and K-d) of 5-HT2(A) serotonin receptors were measured in blood samples drawn from 27 individuals diagnosed with polymyalgia rheumatica and/or giant cell arteritis before and after start of an oral treatment with prednisolone. For each patient B-max and K-d at baseline before prednisolone treatment were compared with B-max and K-d in samples drawn at a first and second follow-up clinic visit at an average of 8.8 (+/- 2.5) days and 33.6 (+/- 6.8) days, respectively. Results: The density of 5-HT2(A) receptors increased after treatment in 23 individuals. The mean B-max value at baseline for all patients was 45.2 fmol/mg protein compared with 64.9 fmol/mg protein in the corresponding samples drawn at the second follow-up visit (p = 0.001). There also was an association between individuals accumulated prednisolone dose and the magnitude of change in B-max between baseline and the first follow-up visit. Erythrocyte sedimentation rate, platelet count or gender had no influence on the results. There were no significant differences in K-d during the treatment period. However, a low K-d value at baseline was a predictor for an increase in B-max following treatment. Conclusions: The results of this study showed that the density of 5-HT2(A) serotonin receptors in man is increased after a subchronic treatment with glucocorticoids. The magnitude of the increase appears to be associated with the affinity of 5-HT2(A) receptors before treatment and the accumulated dose of glucocorticoid early in the treatment period. (C) 2012 Elsevier Ltd. All rights reserved.