Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction
| Autor: | K A Raczka, M-L Mechias, Juergen Deckert, Mathias Pessiglione, Andreas Reif, Nina Gartmann, Raffael Kalisch |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Dopamine medicine.medical_treatment Conditioning Classical Exposure therapy Striatum Neuropsychological Tests Stimulus (physiology) Catechol O-Methyltransferase safety learning Basal Ganglia Extinction Psychological Cellular and Molecular Neuroscience DAT1 conditioning Basal ganglia ventral striatum medicine Humans dopamine transporter Biological Psychiatry Dopamine Plasma Membrane Transport Proteins prediction error medicine.diagnostic_test Ventral striatum Fear social sciences Extinction (psychology) Magnetic Resonance Imaging humanities Associative learning Psychiatry and Mental health medicine.anatomical_structure Original Article Functional magnetic resonance imaging Psychology Neuroscience |
| Zdroj: | Translational Psychiatry |
| ISSN: | 2158-3188 |
| DOI: | 10.1038/tp.2011.10 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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