Open AccessD1- and D2-like receptors differentially mediate the effects of dopaminergic transmission on cost–benefit evaluation and motivation in monkeys
Author(s) -
Yukiko Hori,
Yuji Nagai,
Koki Mimura,
Tetsuya Suhara,
Makoto Higuchi,
Sébastien Bouret,
Takafumi Minamimoto
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001055
Subject(s) - dopaminergic , discounting , biology , neuroscience , blockade , dopamine , macaque , receptor , genetics , finance , economics
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.