Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

Susanne Vogel*, Floris Klumpers, Tobias Navarro Schroeder, Krista T. Oplaat, Harm J. Krugers, Melly S. Oitzl, Marian Joels, Christian F. Doeller, Guillen Fernandez

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    38 Citations (Scopus)

    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 stimulusresponse 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.

    Original languageEnglish
    Pages (from-to)1262-1271
    Number of pages10
    JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
    Volume42
    Issue number6
    DOIs
    Publication statusPublished - May-2017

    Keywords

    • MULTIPLE MEMORY-SYSTEMS
    • EMOTIONAL MODULATION
    • SPATIAL MEMORY
    • HEAD DIRECTION
    • HABIT MEMORY
    • AMYGDALA
    • BRAIN
    • STRATEGIES
    • BLOCKADE
    • RATS

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