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Related Experiment Videos

Do antidepressants regulate how cortisol affects the brain?

Carmine M Pariante1, Sarah A Thomas, Simon Lovestone

  • 1Institute of Psychiatry, King's College London, 1 Windsor Walk, Denmark Hill, London SE5 8AF, UK. spjucmp@iop.kcl.ac.uk

Psychoneuroendocrinology
|January 30, 2004
PubMed
Summary
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Antidepressants may enhance the therapeutic effects by inhibiting steroid transporters. This action increases cortisol access to the brain, improving negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis.

Area of Science:

  • Neuroendocrinology
  • Pharmacology
  • Molecular Biology

Background:

  • Antidepressants influence glucocorticoid hormones and receptors, crucial for therapeutic action.
  • Molecular mechanisms linking antidepressants to glucocorticoid regulation remain unclear.
  • Studies indicate antidepressants enhance glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) function, potentially reducing hypothalamic-pituitary-adrenal (HPA) axis activity.

Purpose of the Study:

  • To review the effects of membrane steroid transporters and antidepressants on corticosteroid receptors.
  • To present new in vitro and in vivo data on GR function and cortisol transport.
  • To propose a mechanism by which antidepressants may enhance HPA axis negative feedback.

Main Methods:

  • In vitro studies of GR live microscopy to observe ligand-induced translocation.

Related Experiment Videos

  • In situ brain perfusion model in anesthetized guinea-pigs to assess blood-brain barrier (BBB) cortisol entry.
  • Analysis of antidepressant effects on membrane steroid transporters in mouse fibroblasts and rat cortical neurons.

    • Main Results:

    • Ligand-induced GR translocation occurs rapidly, within minutes.
    • Cortisol entry into the brain is restricted by the blood-brain barrier (BBB).
    • Chemically diverse antidepressants affect membrane steroid transporters in neuronal and fibroblast models.

    Conclusions:

    • Antidepressants may inhibit BBB and neuronal steroid transporters, such as P-glycoprotein.
    • This inhibition could increase brain cortisol levels, enhancing glucocorticoid-mediated negative feedback on the HPA axis.
    • Boosting brain cortisol action represents a potential strategy to optimize antidepressant therapy.