D(1)- and D(2)-like receptors differentially mediate the effects of dopaminergic transmission on cost–benefit evaluation and motivation in monkeys

It has been widely accepted that dopamine (DA) plays a major role in motivation, yet the specific contribution of DA signaling at D(1)-like receptor (D(1)R) and D(2)-like receptor (D(2)R) to cost–benefit trade-off remains unclear. Here, by combining pharmacological manipulation of DA receptors (DARs) and positron emission tomography (PET) imaging, we assessed the relationship between the degree of D(1)R/D(2)R blockade and changes in benefit- and cost-based motivation for goal-directed behavior of macaque monkeys. We found that the degree of blockade of either D(1)R or D(2)R was associated with a reduction of the positive impact of reward amount and increasing delay discounting. Workload discounting was selectively increased by D(2)R antagonism. In addition, blocking both D(1)R and D(2)R had a synergistic effect on delay discounting but an antagonist effect on workload discounting. These results provide fundamental insight into the distinct mechanisms of DA action in the regulation of the benefit- and cost-based motivation, which have important implications for motivational alterations in both neurological and psychiatric disorders.