title: Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum.
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.
authors.affiliation: 1] Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands [2] Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vogel
authors.affiliation: 1] Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands [2] Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Klumpers
authors.affiliation: University of Amsterdam, Faculty of Science, Amsterdam, The Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Krugers
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Krista T
authors.initials: KT
authors.lastname: Oplaat
authors.affiliation: University of Amsterdam, Faculty of Science, Amsterdam, The Netherlands.
authors.forename: Melly S
authors.initials: MS
authors.lastname: Oitzl
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.affiliation: 1] Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands [2] Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature / Q000009:adverse effects; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D066276:Corticomedial Nuclear Complex / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D005145:Face; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000187:drug effects; D010775:Photic Stimulation; D011930:Reaction Time / Q000187:drug effects; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000008:administration & dosage; D013315:Stress, Psychological / Q000209:etiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D010100:Oxygen; D006854:Hydrocortisone