論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ニホンザル | |