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Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus

Published online by Cambridge University Press:  04 March 2011

J. Kukolja ,
D. Klingmüller ,
W. Maier ,
G. R. Fink  and
R. Hurlemann
J. Kukolja*
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany Department of Neurology, University Hospital, Cologne University, Cologne, Germany
D. Klingmüller
Affiliation:
Department of Clinical Biochemistry, Division of Endocrinology, University of Bonn, Bonn, Germany
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
G. R. Fink
Affiliation:
Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany Department of Neurology, University Hospital, Cologne University, Cologne, Germany
R. Hurlemann
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
*
*Address for correspondence: J. Kukolja, M.D., Department of Neurology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany. (Email: juraj.kukolja@uk-koeln.de)
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Abstract

Background

Current rodent models emphasize the joint action of the stress mediators noradrenaline (NE) and cortisol (CORT) in conferring a memory advantage of emotional over neutral stimuli.

Method

Using a pharmacological strategy of tackling this stress-related mechanism to enhance human episodic (autobiographical) memory, we measured amygdala-hippocampal responses during encoding of emotional and neutral stimuli with functional magnetic resonance imaging in 51 healthy subjects under four pharmacological conditions in a double-blind parallel group design: (i) placebo; (ii) the NE-reuptake inhibitor reboxetine (4 mg); (iii) hydrocortisone (synthetic CORT) (30 mg); or (iv) both agents in combination.

Results

Differential drug effects were found in the left hippocampus, whereas hydrocortisone alone selectively decreased hippocampal responses to emotional relative to neutral stimuli, reboxetine potentiated hippocampal responses to these stimuli. Importantly, the inhibitory influence of hydrocortisone was reversed by co-administration of reboxetine.

Conclusions

Our results imply that stress levels of CORT alone attenuate hippocampal responses to emotional stimuli, an effect possibly related to a regulatory negative feedback loop. However, when simultaneously elevated to stress levels, NE and CORT act together to synergistically enhance hippocampal activity during encoding of emotional stimuli, a mechanism that may turn maladaptive under circumstances of traumatic stress.

Keywords

CortisolemotionfMRIhippocampusmemorynoradrenalinestress
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 10 , October 2011 , pp. 2167 - 2176
Copyright
Copyright © Cambridge University Press 2011

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