Dopamine D3 Receptor Availability Is Associated with Inflexible Decision Making
| Autor: | Yiyun Huang, Bart Massi, Lihui Chen, Jane R. Taylor, Stephanie M. Groman, Jim Ropchan, Evan D. Morris, Nathaniel Smith, Daeyeol Lee, J. Ryan Petrullli |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Male Time Factors medicine.drug_class Decision Making Dopamine Agents Reversal Learning Biology Models Biological Midbrain 03 medical and health sciences 0302 clinical medicine Dopamine receptor D3 Dopamine receptor D2 Oxazines Radioligand medicine Reinforcement learning Animals Computer Simulation Rats Long-Evans Receptor Adaptive behavior Analysis of Variance Brain Mapping General Neuroscience Receptors Dopamine D3 Brain Articles Rats 030104 developmental biology Positron-Emission Tomography Conditioning Operant Food Deprivation Neuroscience 030217 neurology & neurosurgery Protein Binding |
| Popis: | Dopamine D2/3 receptor signaling is critical for flexible adaptive behavior; however, it is unclear whether D2, D3, or both receptor subtypes modulate precise signals of feedback and reward history that underlie optimal decision making. Here, PET with the radioligand [11C]-(+)-PHNO was used to quantify individual differences in putative D3 receptor availability in rodents trained on a novel three-choice spatial acquisition and reversal-learning task with probabilistic reinforcement. Binding of [11C]-(+)-PHNO in the midbrain was negatively related to the ability of rats to adapt to changes in rewarded locations, but not to the initial learning. Computational modeling of choice behavior in the reversal phase indicated that [11C]-(+)-PHNO binding in the midbrain was related to the learning rate and sensitivity to positive, but not negative, feedback. Administration of a D3-preferring agonist likewise impaired reversal performance by reducing the learning rate and sensitivity to positive feedback. These results demonstrate a previously unrecognized role for D3 receptors in select aspects of reinforcement learning and suggest that individual variation in midbrain D3 receptors influences flexible behavior. Our combined neuroimaging, behavioral, pharmacological, and computational approach implicates the dopamine D3 receptor in decision-making processes that are altered in psychiatric disorders. SIGNIFICANCE STATEMENT Flexible decision-making behavior is dependent upon dopamine D2/3 signaling in corticostriatal brain regions. However, the role of D3 receptors in adaptive, goal-directed behavior has not been thoroughly investigated. By combining PET imaging with the D3-preferring radioligand [11C]-(+)-PHNO, pharmacology, a novel three-choice probabilistic discrimination and reversal task and computational modeling of behavior in rats, we report that naturally occurring variation in [11C]-(+)-PHNO receptor availability relates to specific aspects of flexible decision making. We confirm these relationships using a D3-preferring agonist, thus identifying a unique role of midbrain D3 receptors in decision-making processes. |
| Databáze: | OpenAIRE |
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