Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear.
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Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear. / Haaker, Jan; Gaburro, Stefano; Sah, Anupam; Gartmann, Nina; Lonsdorf, Tina B; Meier, Kolja; Singewald, Nicolas; Pape, Hans-Christian; Morellini, Fabio; Kalisch, Raffael.
in: P NATL ACAD SCI USA, Jahrgang 110, Nr. 26, 26, 2013, S. 2428-2436.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear.
AU - Haaker, Jan
AU - Gaburro, Stefano
AU - Sah, Anupam
AU - Gartmann, Nina
AU - Lonsdorf, Tina B
AU - Meier, Kolja
AU - Singewald, Nicolas
AU - Pape, Hans-Christian
AU - Morellini, Fabio
AU - Kalisch, Raffael
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Adult
KW - Amygdala
KW - Animals
KW - Extinction, Psychological
KW - Fear
KW - Humans
KW - Levodopa
KW - Male
KW - Memory
KW - Mice
KW - Mice, Inbred C57BL
KW - Middle Aged
KW - Prefrontal Cortex
U2 - 10.1073/pnas.1303061110
DO - 10.1073/pnas.1303061110
M3 - SCORING: Journal article
C2 - 23754384
VL - 110
SP - 2428
EP - 2436
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 26
M1 - 26
ER -
