Dopamine receptors regulate preference between high-effort and high-risk rewards

Rationale: Optimal decision-making necessitates evaluation of multiple rewards that are each offset by distinct costs, such as high effort requirement or high risk of failure. The neurotransmitter dopamine is fundamental toward these cost-benefit analyses, and D1-like and D2-like dopamine receptors differently modulate the reward-discounting effects of both effort and risk. However, measuring the role of dopamine in regulating decision-making between options associated with distinct costs exceeds the scope of traditional rodent economic decision-making paradigms. Objectives: We developed the effort vs probability economic conflict task (EvP) to model multimodal economic decision-making in rats. This task measures choice between two rewards of uniform magnitude associated with either a high effort requirement or risk of reward omission. We then tested the modulatory effects of systemic cocaine and D1/D2 blockade or activation on the preference between high-effort and high-risk alternatives. Methods: In the EvP, two reinforcers of equal magnitude are associated with either (1) an effort requirement that increases throughout the session (1, 5, 10, and 20 lever presses), or (2) a low probability of reward receipt (25% of probabilistic choices). Critically, the reinforcer for each choice is comparable (one pellet), which eliminates the influence of magnitude discrimination on the decision-making process. After establishing the task, the dopamine transporter blocker cocaine and D1/D2 antagonists and agonists were administered prior to EvP performance. Results: Preference shifted away from either effortful or probabilistic choice when either option became more costly, and this preference was highly variable between subjects and stable over time. Cocaine, D1 activation, and D2 blockade produced limited, dose-dependent shifts in choice preference contingent on high or low effort conditions. In contrast, D2 activation across multiple doses evoked a robust shift from effortful to risky choice that was evident even when clearly disadvantageous. Conclusions: The EvP clearly demonstrates that rats can evaluate distinct effortful or risky costs associated with rewards of comparable magnitude, and shift preference away from either option with increasing cost. This preference is more tightly linked to D2 than D1 receptor manipulation, suggesting D2-like receptors as a possible therapeutic target for maladaptive biases toward risk-taking over effort