Effects of antidepressants on the brain/plasma distribution of corticosterone

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Claudia-Carolin WeberW E Müller

Abstract

It is well established that hypothalamic-pituitary-adrenal (HPA) axis dysregulation, characterized by elevated circulating cortisol concentrations and impaired negative feedback inhibition, is associated with affective disorders. As normalization of the HPA axis function and mood-stabilizing effects occur simultaneously during antidepressant treatment, it is likely that these effects are either directly or indirectly dependent. Although data concerning the outward transport of glucocorticoids from the brain by P-glycoprotein (Pgp) are inconsistent, it has been hypothesized that antidepressants exert their clinical activity in parts by inhibiting Pgp, subsequently leading to enhanced brain glucocorticoid levels and the normalization of the HPA axis function. Here, we report on the effects of different antidepressants (amitriptyline, fluoxetine, mirtazapine, St John's wort extract) on the brain/plasma distribution of corticosterone in mice after acute and subchronic treatment. The four antidepressants exerted different effects on the corticosterone concentration in brain and plasma. Changes in corticosterone levels were highly correlated, suggesting passive diffusion between both tissues. St John's wort extract and fluoxetine ele...Continue Reading

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Mar 16, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joyce L W YauCarmine M Pariante
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Jan 2, 2021·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Igor Branchi, Alessandro Giuliani

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