title: Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.
abstract: Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.|Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.|Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Klumpers
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
authors.forename: Tobias Navarro
authors.initials: TN
authors.lastname: Schröder
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.|Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Krista T
authors.initials: KT
authors.lastname: Oplaat
authors.affiliation: Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Krugers
authors.affiliation: Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Melly S
authors.initials: MS
authors.lastname: Oitzl
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Translational Neuroscience, Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Doeller
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.|Radboud University Medical Center, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernández
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D063132:Connectome; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D006854:Hydrocortisone