1. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.
- Author
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Vogel S, Klumpers F, Schröder TN, Oplaat KT, Krugers HJ, Oitzl MS, Joëls M, Doeller CF, and Fernández G
- Subjects
- Adult, Amygdala diagnostic imaging, Amygdala drug effects, Humans, Magnetic Resonance Imaging, Male, Memory Disorders etiology, Mineralocorticoid Receptor Antagonists administration & dosage, Neostriatum diagnostic imaging, Neostriatum drug effects, Spatial Learning drug effects, Stress, Psychological metabolism, Young Adult, Amygdala physiopathology, Connectome, Hydrocortisone metabolism, Memory Disorders physiopathology, Mineralocorticoid Receptor Antagonists pharmacology, Neostriatum physiopathology, Receptors, Mineralocorticoid metabolism, Spatial Learning physiology, Stress, Psychological complications
- 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.
- Published
- 2017
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