Social Cognitive and Affective Neuroscience Advance Access originally published online on February 25, 2009
Social Cognitive and Affective Neuroscience 2009 4(2):119-126; doi:10.1093/scan/nsn049
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Noradrenergic enhancement of amygdala responses to fear
1Department of Psychiatry, University of Bonn, 53105 Bonn 2Brain Imaging Center West 3Institute of Neuroscience and Biophysics – Medicine (INB3), Research Center Juelich, 52425 Juelich 4Division of Medical Psychology, University of Bonn, 53105 Bonn, Germany 5Departments of Psychiatry and Behavioral Sciences, The Johns Hopkins University, Baltimore, MD 21287-7413, USA,and 6BCN NeuroImaging Center, University Medical Center Groningen, University of Groningen, 9713 AW Groningen, The Netherlands
Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no causative link between elevated NE neurotransmission and BLA hyperresponsiveness to fear signals has been established to date in humans. To determine whether or not increased noradrenergic tone enhances BLA responses to fear signals, we used functional magnetic resonance imaging (fMRI) and a strategy of pharmacologically potentiating NE neurotransmission in healthy volunteers. 18 subjects were scanned two times on a facial emotion paradigm and given either a single-dose placebo or 4 mg of the selective NE reuptake inhibitor reboxetine 2 h prior to an fMRI session. We found that reboxetine induced an amygdala response bias towards fear signals that did not exist at placebo baseline. This pharmacological effect was probabilistically mapped to the BLA. Extrapolation of our data to conditions of traumatic stress suggests that disinhibited endogenous NE signaling could serve as a crucial etiological contributor to post-traumatic stress disorder (PTSD) by eliciting exaggerated BLA responses to fear signals.
Keywords: amygdala; emotion; face; fear; fMRI; noradrenaline; reboxetine
Correspondence should be addressed to René Hurlemann, MSc, MD, PhD, Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. E-mail: renehurlemann{at}me.com
Received October 14, 2008. Accepted November 13, 2008.