Noradrenergic enhancement of amygdala responses to fear.
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.
Onur
Oezguer A
OA
Department of Psychiatry, University of Bonn, 53105 Bonn, Germany.
Walter
Henrik
H
Schlaepfer
Thomas E
TE
Rehme
Anne K
AK
Schmidt
Christoph
C
Keysers
Christian
C
Maier
Wolfgang
W
Hurlemann
René
R
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D001931:Brain Mapping; D004311:Double-Blind Method; D019260:Expressed Emotion / Q000187:drug effects; D005239:Fear; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D000077593:Reboxetine; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D000077593:Reboxetine; D010100:Oxygen; D009638:Norepinephrine