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Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol

Published online by Cambridge University Press:  27 January 2010

R. Hurlemann*
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany
H. Walter
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Division of Medical Psychology, University of Bonn, Bonn, Germany
A. K. Rehme
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
J. Kukolja
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany
S. C. Santoro
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
C. Schmidt
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
K. Schnell
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Division of Medical Psychology, University of Bonn, Bonn, Germany
F. Musshoff
Affiliation:
Institute of Legal Medicine, University of Bonn, Bonn, Germany
C. Keysers
Affiliation:
BCN NeuroImaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
K. M. Kendrick
Affiliation:
Cognitive and Behavioral Neuroscience, The Babraham Institute, Babraham, Cambridge, UK
O. A. Onur
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany
*
*Address for correspondence: Dr R. Hurlemann, Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105Bonn, Germany. (Email: renehurlemann@me.com)

Abstract

Background

Animal models of anxiety disorders emphasize the crucial role of locus ceruleus–noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a β-noradrenergic receptor blockade with propranolol in the alleviation of anxiety symptoms and the secondary prevention of post traumatic stress disorder, preclinical evidence for a β-noradrenergic modulation of BLA activity in humans is missing.

Method

We combined functional magnetic resonance imaging in healthy volunteers with probabilistic mapping of intra-amygdalar responses to fearful, neutral and happy facial expressions to test the hypothesis that a β-noradrenergic receptor blockade with propranolol would inactivate the BLA.

Results

Consistent with our a priori hypothesis, propranolol diminished BLA responses to facial expressions, independent of their emotional valence. The absence of activity changes in probabilistically defined visual control regions underscores the specific action of propranolol in the BLA.

Conclusions

Our findings provide the missing link between the anxiolytic potential of propranolol and the biological basis of β-noradrenergic activation in the human BLA as a key target for the pharmacological inhibition of anxiety neurocircuitry. Moreover, our findings add to emerging evidence that NE modulates both the reactivity (sensitivity) and the operating characteristics (specificity) of the BLA via β-noradrenergic receptors.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2010

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