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


METHODS
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.
Hurlemann
R
R
Department of Psychiatry, University of Bonn, Bonn, Germany. renehurlemann@me.com
Walter
H
H
Rehme
A K
AK
Kukolja
J
J
Santoro
S C
SC
Schmidt
C
C
Schnell
K
K
Musshoff
F
F
Keysers
C
C
Maier
W
W
Kendrick
K M
KM
Onur
O A
OA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D005149:Facial Expression; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D006240:Happiness; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D055815:Young Adult
D000319:Adrenergic beta-Antagonists; D011433:Propranolol