Psychological Medicine

Original Articles

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

R. Hurlemanna1a6 c1, H. Waltera1a2, A. K. Rehmea1, J. Kukoljaa1a6, S. C. Santoroa1, C. Schmidta1, K. Schnella1a2, F. Musshoffa3, C. Keysersa4, W. Maiera1, K. M. Kendricka5 and O. A. Onura1a6

a1 Department of Psychiatry, University of Bonn, Bonn, Germany

a2 Division of Medical Psychology, University of Bonn, Bonn, Germany

a3 Institute of Legal Medicine, University of Bonn, Bonn, Germany

a4 BCN NeuroImaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

a5 Cognitive and Behavioral Neuroscience, The Babraham Institute, Babraham, Cambridge, UK

a6 Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany

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.

(Received June 22 2009)

(Revised December 04 2009)

(Accepted December 09 2009)

(Online publication January 27 2010)

Correspondence

c1 Address for correspondence: Dr R. Hurlemann, Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. (Email: renehurlemann@me.com)

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