D1- and D2-like receptors differentially mediate the effects of dopaminergic transmission on cost–benefit evaluation and motivation in monkeys |
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Authors: | Yukiko Hori Yuji Nagai Koki Mimura Tetsuya Suhara Makoto Higuchi Sebastien Bouret Takafumi Minamimoto |
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Affiliation: | 1. Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan;2. Team Motivation Brain & Behavior, Institut du Cerveau et de la Moelle épinière (ICM), Centre National de la Recherche Scientifique (CNRS), Hôpital Pitié Salpêtrière, Paris, France;Oxford University, UNITED KINGDOM |
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Abstract: | 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 (PET) 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 the positive impact of reward amount and increasing delay discounting. Workload discounting was selectively increased by D2R antagonism. In addition, blocking both D1R and D2R 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.Using quantitatively controlled pharmacological manipulations, this study teases apart the role of D1- and D2-like dopamine receptors in motivation and goal-directed behavior in monkeys, revealing complementary roles of two dopamine receptor subtypes in the computation of the cost/benefit trade-off to guide action. |
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