PT - JOURNAL ARTICLE AU - Yukiko Hori AU - Yuji Nagai AU - Koki Mimura AU - Tetsuya Suhara AU - Makoto Higuchi AU - Sebastien Bouret AU - Takafumi Minamimoto TI - Differential Contribution of Dopaminergic Transmission at D<sub>1</sub>- and D<sub>2</sub>-like Receptors to Cost/Benefit Evaluation for Motivation in Monkeys AID - 10.1101/2020.11.27.400911 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.27.400911 4099 - http://biorxiv.org/content/early/2020/11/27/2020.11.27.400911.short 4100 - http://biorxiv.org/content/early/2020/11/27/2020.11.27.400911.full AB - 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.