| Summary: | Weighing the value of a reward against its likelihood of delivery is a necessary component of adaptive decision-making. The medial subregion of the orbitofrontal cortex (OFC) plays a key role in this form of cognition, as inactivation of this subregion in rats alters behaviour during risk/reward decision-making and a probabilistic assay of cognitive flexibility. The medial OFC receives dopaminergic input from midbrain neurons, yet whether dopamine (DA) modulates medial OFC function has been virtually unexplored. Here, we assessed how D₁ and D₂ receptors in the medial OFC may modulate adaptive decision-making in the face of probabilistic outcomes. One series of experiments assessed probabilistic reversal learning, while another set of studies assessed risk/reward decision-making using a probabilistic discounting task. Separate groups of well-trained rats, received intra-medial OFC microinfusions of selective D₁ or D₂ antagonists prior to task performance. Our results indicate that blocking D₁ receptors in the medial OFC impaired while blockade of D₂ receptors facilitated the number of reversals completed. This may be due to an impairment in probabilistic reinforcement learning, as effects were mediated by changes in errors during the initial discrimination of the task. One function for DA within the medial OFC might therefore be to inform about responses that yield a higher probability of reward over less profitable options to maintain adaptive choice. During risk/reward decision-making, blocking D₁ receptors reduced risky choice driven by an increase in negative feedback sensitivity. Blockade of D₂ receptors increased risky choice, mediated instead by an increase in reward sensitivity. This implicates medial OFC DA in dampening the win-stay/lose-shift strategy to limit the use of immediate reward feedback in situations where rats have prior knowledge about reward profitability. These findings highlight a novel role for medial OFC DA in guiding behavior in situations of reward uncertainty. Medial OFC D₁ and D₂ receptors play dissociable and opposing roles in different forms of reward-related action selection. Elucidating how DA within different nodes of mesocorticolimbic circuitry biases behavior in these situations will expand our understanding of the mechanisms regulating optimal and aberrant decision-making. === Arts, Faculty of === Psychology, Department of === Graduate
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