Medial orbitofrontal cortex dopamine D/D receptors differentially modulate distinct forms of probabilistic decision-making.

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 D and D 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 D or D antagonists or agonists prior to task performance. mOFC D and D blockade had opposing effects on performance during probabilistic reversal learning and probabilistic discounting. D blockade impaired, while D 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, D blockade reduced, while D blockade increased preference for larger/risky rewards. Excess D stimulation had no effect on either task, while excessive D 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 D and D 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.