TY - JOUR
T1 - Dopamine D3 receptor availability is associated with inflexible decision making
AU - Groman, Stephanie M.
AU - Smith, Nathaniel J.
AU - Petrullli, J. Ryan
AU - Massi, Bart
AU - Chen, Lihui
AU - Ropchan, Jim
AU - Huang, Yiyun
AU - Lee, Daeyeol
AU - Morris, Evan D.
AU - Taylor, Jane R.
N1 - Publisher Copyright:
© 2016 the authors.
PY - 2016/6/22
Y1 - 2016/6/22
N2 - 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.
AB - 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.
KW - Addiction
KW - Computational analyses
KW - Decision-making
KW - Dopamine D receptors
KW - PET
KW - Reinforcement learning
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U2 - 10.1523/JNEUROSCI.3253-15.2016
DO - 10.1523/JNEUROSCI.3253-15.2016
M3 - Article
C2 - 27335404
AN - SCOPUS:84975231527
SN - 0270-6474
VL - 36
SP - 6732
EP - 6741
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 25
ER -