title: Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.
abstract: BACKGROUND
  Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR.
  
  
  METHODS
  Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum.
  
  
  RESULTS
  Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance.
  
  
  CONCLUSIONS
  Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR.
authors.affiliation: Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr-University Bochum, Bochum, Germany. Electronic address: Lars.Schwabe@ruhr-uni-bochum.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Schwabe
authors.forename: Martin
authors.initials: M
authors.lastname: Tegenthoff
authors.forename: Oliver
authors.initials: O
authors.lastname: Höffken
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Wolf
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013148:Spironolactone / Q000494:pharmacology*; D013312:Stress, Physiological; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D006854:Hydrocortisone
keywords: Dorsal striatum; glucocorticoids; hippocampus; memory systems; mineralocorticoid receptor; stress