| RRC ID |
80062
|
| 著者 |
Hori Y, Mimura K, Nagai Y, Hori Y, Kumata K, Zhang MR, Suhara T, Higuchi M, Minamimoto T.
|
| タイトル |
Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys.
|
| ジャーナル |
PLoS Biol
|
| Abstract |
Serotonin (5-HT) deficiency is a core biological pathology underlying depression and other psychiatric disorders whose key symptoms include decreased motivation. However, the exact role of 5-HT in motivation remains controversial and elusive. Here, we pharmacologically manipulated the 5-HT system in macaque monkeys and quantified the effects on motivation for goal-directed actions in terms of incentives and costs. Reversible inhibition of 5-HT synthesis increased errors and reaction times on goal-directed tasks, indicating reduced motivation. Analysis found incentive-dependent and cost-dependent components of this reduction. To identify the receptor subtypes that mediate cost and incentive, we systemically administered antagonists specific to 4 major 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4. Positron emission tomography (PET) visualized the unique distribution of each subtype in limbic brain regions and determined the systemic dosage for antagonists that would achieve approximately 30% occupancy. Only blockade of 5-HT1A decreased motivation through changes in both expected cost and incentive; sensitivity to future workload and time delay to reward increased (cost) and reward value decreased (incentive). Blocking the 5-HT1B receptor also reduced motivation through decreased incentive, although it did not affect expected cost. These results suggest that 5-HT deficiency disrupts 2 processes, the subjective valuation of costs and rewards, via 5-HT1A and 5-HT1B receptors, thus leading to reduced motivation.
|
| 巻・号 |
22(1)
|
| ページ |
e3002445
|
| 公開日 |
2024-1-1
|
| DOI |
10.1371/journal.pbio.3002445
|
| PII |
PBIOLOGY-D-23-00497
|
| PMID |
38163325
|
| PMC |
PMC10758260
|
| MeSH |
Animals
Brain / metabolism
Carrier Proteins / metabolism
Macaca
Receptor, Serotonin, 5-HT1B
Serotonin*
Serotonin Antagonists* / pharmacology
|
| IF |
7.076
|
| リソース情報 |
| ニホンザル |
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