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Hori, Yukiko; Nagai, Yuji; Mimura, Koki; Suhara, Tetsuya; Higuchi, Makoto; Bouret, Sebastien; Minamimoto, Takafumi
PLoS biology, 07/2021, Volume: 19, Issue: 7Journal Article
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.
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