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Medial orbitofrontal cortex dopamine D1/D2 receptors differentially modulate distinct forms of probabilistic decision-making

Abstract

Efficient decision-making involves weighing the costs and benefits associated with different actions and outcomes to maximize long-term utility. The medial orbitofrontal cortex (mOFC) has been implicated in guiding choice in situations involving reward uncertainty, as inactivation in rats alters choice involving probabilistic rewards. The mOFC receives considerable dopaminergic input, yet how dopamine (DA) modulates mOFC function has been virtually unexplored. Here, we assessed how mOFC D1 and D2 receptors modulate two forms of reward seeking mediated by this region, probabilistic reversal learning and probabilistic discounting. Separate groups of well-trained rats received intra-mOFC microinfusions of selective D1 or D2 antagonists or agonists prior to task performance. mOFC D1 and D2 blockade had opposing effects on performance during probabilistic reversal learning and probabilistic discounting. D1 blockade impaired, while D2 blockade increased the number of reversals completed, both mediated by changes in errors and negative feedback sensitivity apparent during the initial discrimination of the task, which suggests changes in probabilistic reinforcement learning rather than flexibility. Similarly, D1 blockade reduced, while D2 blockade increased preference for larger/risky rewards. Excess D1 stimulation had no effect on either task, while excessive D2 stimulation impaired probabilistic reversal performance, and reduced both profitable risky choice and overall task engagement. These findings highlight a previously uncharacterized role for mOFC DA, showing that D1 and D2 receptors play dissociable and opposing roles in different forms of reward-related action selection. Elucidating how DA biases behavior in these situations will expand our understanding of the mechanisms regulating optimal and aberrant decision-making.

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Fig. 1: Task procedures and histology.
Fig. 2: Blockade of D1 vs D2 receptors within mOFC differentially alters probabilistic reversal learning.
Fig. 3: Effects of stimulation of mOFC D1 and D2 receptors on probabilistic reversal performance.
Fig. 4: Blockade of D1 and D2 receptors within the mOFC differentially impairs probabilistic discounting.
Fig. 5: Effects of DA agonist  in the mOFC on probabilistic discounting and reward magnitude discrimination.

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NLJ and YTL acquired the data. NLJ and SBF designed the study, analyzed the data, and wrote the manuscript.

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Correspondence to Stan B. Floresco.

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Jenni, N.L., Li, Y.T. & Floresco, S.B. Medial orbitofrontal cortex dopamine D1/D2 receptors differentially modulate distinct forms of probabilistic decision-making. Neuropsychopharmacol. 46, 1240–1251 (2021). https://doi.org/10.1038/s41386-020-00931-1

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