Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

Susanne Vogel, Floris Klumpers, Harm J. Krugers, Zhou Fang, Krista T. Oplaat, Melly S. Oitzl, Marian Joels, Guillen Fernandez*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

56 Citations (Scopus)

Abstract

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol.

Original languageEnglish
Pages (from-to)947-956
Number of pages10
JournalNeuropsychopharmacology
Volume40
Issue number4
DOIs
Publication statusPublished - Mar-2015
Externally publishedYes

Keywords

  • MULTIPLE MEMORY-SYSTEMS
  • FUNCTIONAL CONNECTIVITY
  • BASOLATERAL AMYGDALA
  • INDUCED MODULATION
  • BRAIN
  • CORTICOSTERONE
  • RESPONSES
  • BLOCKADE
  • FEAR
  • MEN

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