Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 26, Pages E2428-E2436Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1303061110
Keywords
fear conditioning; psychotherapy; reinstatement; renewal; resilience
Categories
Funding
- Deutsche Forschungsgemeinschaft [KA1623/3-1, KA1623/4-1, SFB-TR58 A03]
- State of Hamburg excellence initiative (neurodapt! consortium)
- Austrian Science Fund (Fonds zur Forderung der Wissenschaftlichen Forschung)
- Signal Processing in Neurons [W1206-B18]
- [Sonderforschungsbereich F4410]
- Austrian Science Fund (FWF) [W1206] Funding Source: Austrian Science Fund (FWF)
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Traumatic events can engender persistent excessive fear responses to trauma reminders that may return even after successful treatment. Extinction, the laboratory analog of behavior therapy, does not erase conditioned fear memories but generates competing, fear-inhibitory extinction memories that, however, are tied to the context in which extinction occurred. Accordingly, a dominance of fear over extinction memory expression-and, thus, return of fear-is often observed if extinguished fear stimuli are encountered outside the extinction (therapy) context. We show that postextinction administration of the dopamine precursor L-dopa makes extinction memories context-independent, thus strongly reducing the return of fear in both mice and humans. Reduced fear is accompanied by decreased amygdala and enhanced ventromedial prefrontal cortex activation in both species. In humans, ventromedial prefrontal cortex activity is predicted by enhanced resting-state functional coupling of the area with the dopaminergic midbrain during the postextinction consolidation phase. Our data suggest that dopamine-dependent boosting of extinction memory consolidation is a promising avenue to improving anxiety therapy.
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