Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction
Open Access
- 7 June 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Translational Psychiatry
- Vol. 1 (6), e12
- https://doi.org/10.1038/tp.2011.10
Abstract
Exposure therapy for anxiety disorders relies on the principle of confronting a patient with the triggers of his fears, allowing him to make the unexpected safety experience that his fears are unfounded and resulting in the extinction of fear responses. In the laboratory, fear extinction is modeled by repeatedly presenting a fear-conditioned stimulus (CS) in the absence of the aversive unconditioned stimulus (UCS) to which it had previously been associated. Classical associative learning theory considers extinction to be driven by an aversive prediction error signal that expresses the expectation violation when not receiving an expected UCS and establishes a prediction of CS non-occurrence. Insufficiencies of this account in explaining various extinction-related phenomena could be resolved by assuming that extinction is an opponent appetitive-like learning process that would be mediated by the mesostriatal dopamine (DA) system. In accordance with this idea, we find that a functional polymorphism in the DA transporter gene, DAT1, which is predominantly expressed in the striatum, significantly affects extinction learning rates. Carriers of the 9-repeat (9R) allele, thought to confer enhanced phasic DA release, had higher learning rates. Further, functional magnetic resonance imaging revealed stronger hemodynamic appetitive prediction error signals in the ventral striatum in 9R carriers. Our results provide a first hint that extinction learning might indeed be conceptualized as an appetitive-like learning process and suggest DA as a new candidate neurotransmitter for human fear extinction. They open up perspectives for neurobiological therapy augmentation.Keywords
This publication has 71 references indexed in Scilit:
- Infralimbic D2 Receptors Are Necessary for Fear Extinction and Extinction-Related Tone ResponsesBiological Psychiatry, 2010
- D-Cycloserine Facilitation of Fear Extinction and Exposure-Based Therapy Might Rely on Lower-Level, Automatic MechanismsBiological Psychiatry, 2009
- Neuropeptide S-Mediated Control of Fear Expression and Extinction: Role of Intercalated GABAergic Neurons in the AmygdalaNeuron, 2008
- Learning affective values for faces is expressed in amygdala and fusiform gyrusSocial Cognitive and Affective Neuroscience, 2008
- Identification and Characterization of Shared Duplications between Rice and Wheat Provide New Insight into Grass Genome EvolutionPlant Cell, 2008
- Gene–gene interaction associated with neural reward sensitivityProceedings of the National Academy of Sciences of the United States of America, 2007
- Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memoriesMolecular Psychiatry, 2007
- A 1,000-loci transcript map of the barley genome: new anchoring points for integrative grass genomicsTheoretical and Applied Genetics, 2007
- Dopamine-dependent prediction errors underpin reward-seeking behaviour in humansNature, 2006
- Transcriptome Analysis of Cold Acclimation in Barley Albina and Xantha MutantsPlant Physiology, 2006