Stress Research: Past, Present, and Future


This chapter starts with highlighting the evolution of the stress concept and the discovery of mediators that coordinate stress adaptation. Next, progress in the unraveling of the mechanism underlying the action of these stress mediators is discussed, focusing on glucocorticoids as the end product of the hypothalamic pituitary adrenal (HPA) axis. This action exerted by the glucocorticoids is mediated by a dual receptor system: mineralocorticoid (MR) and glucocorticoid receptors (GR). With these receptors as leading theme we present five highlights that illustrate the serendipitous nature of stress research. These five highlights are integrated in the final section which culminates in reflections on the role of stress in mental health. In these reflections we merge the mind-boggling complexity of molecular signaling pathways with neuroendocrine communication integrating body and brain functions. The new insights will be used during the next decennium to target, in an individual-specific fashion, the stress system with the objective to enhance the quality of life.



Adrenocorticotropic hormone








Basolateral amygdala


Corticotropin releasing hormone




Extracellular regulated kinase 1/2




Glucocorticoid receptor

HPA axis

Hypothalamic-Pituitary-Adrenal axis


5-Hydroxytryptamine = serotonine


Serotonin transporter


Long-term potentiation


Mineralocorticoid receptor


Multidrug resistance


Miniature excitatory postsynaptic current




Prepulse inhibition


Paraventricular nucleus


Stress hyporesponsive period


Single nucleotide polymorphism



The support by the Royal Netherlands Academy of Arts and Sciences (KNAW), Top Institute-Pharma (TI-Pharma), the Netherlands Scientific Organization (NWO), Human Frontiers in Science program (HFSP) and EU-Eurostress/Eurocores & EU-Lifespan is gratefully acknowledged.

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Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Medical PharmacologyLACDR/LUMC, Leiden UniversityLeidenThe Netherlands
  2. 2.Department of Neuroscience and PharmacologyUniversity Medical Center Utrecht Rudolf Magnus Institute of NeuroscienceUtrechtThe Netherlands

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