Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences

Background Activation of D1 receptors has been related to successful goal-directed behavior, but it remains unclear whether D1 receptor activation causally tips the balance of weighing costs and benefits in humans. Here, we tested the impact of pharmacologically stimulated D1 receptors on sensitivity to risk, delay, and effort costs in economic choice and investigated whether D1 receptor stimulation would bias preferences toward options with increased costs in a cost-specific manner. Methods In a randomized, double-blind, placebo-controlled, parallel-group phase 1 study, 120 healthy young volunteers received either placebo or 1 of 3 doses (6 mg, 15 mg, or 30 mg) of a novel, selective D1 agonist (PF-06412562). After drug administration, participants performed decision tasks measuring their preferences for risky, delayed, and effortful outcomes. Results Higher doses of the D1 agonist increased the willingness to exert physical effort for reward as well as reduced the preference for risky outcomes. We observed no effects on preferences for delayed rewards. Conclusions The current results provide evidence that D1 receptor stimulation causally affects core aspects of cost-benefit decision making in humans.