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 threechoice 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.
Bibliographical noteFunding Information:
This work was supported by Public Health Service Grants DA011717 and DA027844 to J.R.T., Distinguished Investigator National Alliance for Research on Schizophrenia and Depression Award to J.R.T., Yale Center for Clinical Investigation UL1 TR000142, Research Training Biological Sciences Grant 5T32 MH14276 to S.M.G., and National Science Foundation Graduate Research Fellowship DGE-1122492 to J.R.P.Wethank Dr. Edythe London for providing additional imaging software necessary for completing these studies.
- Computational analyses
- Dopamine D receptors
- Reinforcement learning