Differential Contribution of Dopaminergic Transmission at D1- and D2-like Receptors to Cost/Benefit Evaluation for 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 D1-like receptor (D1R) and D2-like receptor (D2R) to cost-benefit trade-off remains unclear. Here, by combining pharmacological manipulation of DA receptors (DARs) and positron emission tomography imaging, we assessed the relationship between the degree of D1R/D2R 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 D1R or D2R was associated with a reduction of relative incentive effect of reward amount, where D2R blockade had a stronger effect. Workload-discounting was selectively increased by D2R antagonism, whereas delay-discounting was similarly increased after D1R and D2R blockades. These results provide fundamental insight into the specific actions of DARs in the regulation of the cost/benefit trade-off and important implications for motivational alterations in both neurological and psychiatric disorders.