A Stress-Induced Shift From Trace to Delay Conditioning Depends on the Mineralocorticoid Receptor

Vogel, Susanne; Klumpers, Floris; Kroes, Marijn C. W.; Oplaat, Krista T.; Krugers, Harm J.; Oitzl, Melly S.; Joëls, Marian; Fernández, Guillén

doi:10.1016/j.biopsych.2015.02.014

Cited by 42 publications

(48 citation statements)

References 71 publications

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“…The current study was part of a large-scale study investigating stress-effects depending on MR-availability. Two other data sets acquired in the same participants using independent tasks investigated the role of the MR in emotional face processing (Vogel et al, 2015b) and fear learning (Vogel et al, 2015a). Thus, the overall study set-up was described elsewhere and is only briefly summarized here, focusing on the spatial memory experiment.…”

Section: Methodsmentioning

confidence: 99%

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

Vogel

Klumpers

Schröder

et al. 2016

Neuropsychopharmacol

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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.

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Section: Methodsmentioning

confidence: 99%

“…Three participants were excluded due to either panic attacks, motion sickness, or the discovery of concurrent participation in another drug study. This resulted in a final number of 98 participants (mean age 21.9 years (SD = 2.9)) not differing in age, body-mass-index, or trait anxiety (Vogel et al, 2015a(Vogel et al, , 2015b.…”

Section: Participantsmentioning

confidence: 99%

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

Vogel

Klumpers

Schröder

et al. 2016

Neuropsychopharmacol

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“…In the second behavioural and psychophysiological session, a probabilistic reversal learning task (Den Ouden et al, 2013) and fear conditioning retention test are administered, to test cognitive flexibility and fear retention from the previous fear-conditioning task, respectively. Finally, during the second fMRI session, (neural) control over emotional actions is investigated with an approach–avoidance task (Roelofs, Minelli, Mars, Van Peer, & Toni, 2009), and resting-state scans are obtained before and after stress induction (Vogel et al, 2015), to assess stress-related alterations in resting-state networks. Saliva samples for endocrinological analyses are collected before the second MRI session, and at several time-points before and after the stress induction to assess stress reactivity.…”

Section: Methodsmentioning

confidence: 99%

“…To assess stress-induced changes in autonomic and HPA axis responding, and associated alterations in functional connectivity networks, resting-state scans are acquired before and after stress induction using the Socially Evaluated Cold Pressor Task (SECPT) and mental arithmetic (MA) task (Schwabe, Haddad, & Schachinger, 2008; Vogel et al, 2015). During the stress induction, participants immerse their right foot in ice water (0–3°C) for as long as possible, with a maximum of three minutes.…”

Section: Methodsmentioning

confidence: 99%

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The role of automatic defensive responses in the development of posttraumatic stress symptoms in police recruits: protocol of a prospective study

Koch

Klumpers

Zhang

et al. 2017

European Journal of Psychotraumatology

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Background: Control over automatic tendencies is often compromised in challenging situations when people fall back on automatic defensive reactions, such as freeze – fight – flight responses. Stress-induced lack of control over automatic defensive responses constitutes a problem endemic to high-risk professions, such as the police. Difficulties controlling automatic defensive responses may not only impair split-second decisions under threat, but also increase the risk for and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the significance of these automatic defensive responses in the development and maintenance of trauma-related symptoms remains unclear due to a shortage of large-scale prospective studies. Objective: The ‘Police-in-Action’ study is conducted to investigate the role of automatic defensive responses in the development and maintenance of PTSD symptomatology after trauma exposure. Methods: In this prospective study, 340 police recruits from the Dutch Police Academy are tested before (wave 1; pre-exposure) and after (wave 2; post-exposure) their first emergency aid experiences as police officers. The two waves of data assessment are separated by approximately 15 months. To control for unspecific time effects, a well-matched control group of civilians (n = 85) is also tested twice, approximately 15 months apart, but without being frequently exposed to potentially traumatic events. Main outcomes are associations between (changes in) behavioural, psychophysiological, endocrine and neural markers of automatic defensive responses and development of trauma-related symptoms after trauma exposure in police recruits. Discussion: This prospective study in a large group of primary responders enables us to distinguish predisposing from acquired neurobiological abnormalities in automatic defensive responses, associated with the development of trauma-related symptoms. Identifying neurobiological correlates of (vulnerability for) trauma-related psychopathology may greatly improve screening for individuals at risk for developing PTSD symptomatology and offer valuable targets for (early preventive) interventions for PTSD.

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High‐dose spironolactone lacks effectiveness in treatment of fibromyalgia (RCT)

Böhm¹,

Westermann

Gleim

et al. 2021

European Journal of Pain

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A Stress-Induced Shift From Trace to Delay Conditioning Depends on the Mineralocorticoid Receptor

Cited by 42 publications

References 71 publications

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

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

The role of automatic defensive responses in the development of posttraumatic stress symptoms in police recruits: protocol of a prospective study

High‐dose spironolactone lacks effectiveness in treatment of fibromyalgia (RCT)

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