Elsevier

Biological Psychiatry

Volume 74, Issue 11, 1 December 2013, Pages 801-808
Biological Psychiatry

Priority Communication
Mineralocorticoid Receptor Blockade Prevents Stress-Induced Modulation of Multiple Memory Systems in the Human Brain

https://doi.org/10.1016/j.biopsych.2013.06.001Get rights and content

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.

Section snippets

Participants and Design

Eighty healthy, right-handed, nonsmoking university students with normal or corrected to normal vision and without any current medical conditions, medication intake, lifetime history of any neurological or psychiatric disorders, or any contraindications for magnetic resonance imaging participated in this experiment (age: mean = 24.6 years, SEM = .3 years). All participants provided written informed consent for participation in the study, which was approved by the ethics committee of the medical

Subjective and Physiological Measures

Changes in subjective feeling, blood pressure, and salivary cortisol verified the successful stress induction. Participants who underwent the SECPT rated the treatment as significantly more stressful, painful, and unpleasant than participants who underwent the control manipulation (all F > 120, all p < .001). Moreover, systolic and diastolic blood pressure increased in response to the SECPT but not in response to the control manipulation (treatment × time point of measurement interactions: both

Discussion

The present findings show for the first time in humans the critical role of the MR in the modulatory effect of stress on the engagement of multiple memory systems. Our results confirm previous studies suggesting a shift from hippocampus-dependent declarative to dorsal striatum-dependent procedural learning after stress 19, 20, 28. Stress (after placebo) reduced declarative task knowledge and increased the use of procedural multi-cue strategies. In addition, dorsal striatal activation correlated

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