D2 dopamine receptor expression, reactivity to rewards, and reinforcement learning in a complex value-based decision-making task.

Different dopamine subtypes have opposing dynamics at post-synaptic receptors, with the ratio of D1 to D2 receptors determining the relative sensitivity to gains and losses, respectively, during value-based learning. This effective sensitivity to different reward feedback interacts with phasic dopamine levels to determine the effectiveness of learning, particularly in dynamic feedback situations where frequency and magnitude of rewards need to be integrated over time to make optimal decisions. We modeled this effect in simulations of the underlying basal ganglia pathways and then tested the predictions in individuals with a variant of the human dopamine receptor D2 (DRD2; -141C Ins/Del and Del/Del) gene that associates with lower levels of D2 receptor expression (N=119) and compared their performance in the Iowa Gambling Task (IGT) to non-carrier controls (N=319). Ventral striatal (VS) reactivity to rewards was measured in the Cards task with fMRI. DRD2 variant carriers made less effective decisions than non-carriers, but this effect was not moderated by VS reward reactivity as is hypothesized by our model. These results suggest that the interaction between dopamine receptor subtypes and reactivity to rewards during learning may be more complex than originally thought.