Roles of dopamine and serotonin in regulating motivation

2022 Fiscal Year Final Research Report

• Project/Area Number: 18H04037
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: Minamimoto Takafumi 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 上席研究員 (50506813)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: ドーパミン / セロトニン / 意欲 / 報酬 / 価値 / 化学遺伝学

Outline of Final Research Achievements

We investigated the mechanisms of motivation regulation involving dopamine and serotonin in macaque monkeys as a model for humans. Dopamine transmission was found to be involved in two distinct mechanisms of motivation regulation mediated by D1 and D2 receptors. In addition, we showed that serotonin transmission, specifically the reduction of serotonin signaling through 5-HT1B and 5-HT1A receptors, leads to a decrease in motivation that is dependent or independent of reward value, respectively. Together with the localization of these receptor subtypes, our findings provided insights into the neural circuits involved. Moreover, we advanced the application of chemogenetics, DREADDs, in macaque monkeys and successfully achieved selective and reversible control of dopamine neuron activity. These achievements hold great promise for advancing our understanding of monoamine control of motivation and the pathophysiology of mental disorders.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

意欲制御の神経機構についてはドーパミンと腹側線条体を中心とするネットワークが関与することが知られている。一方で，意欲低下という症候を引き起こす「うつ」などの病態の背景にドーパミンとセロトニンレベルの低下が示唆されている．しかし，セロトニン低下が引き起こす意欲低下について，意欲制御の神経機構との関連から調べた研究はない。本成果によりドーパミンとセロトニン伝達低下がそれぞれもたらす意欲低下が数理モデルで説明できた。これらのモデルは正常から病態まで一貫して説明する意欲制御の神経機構を提供し、精神・神経疾患の病態理解の進展が期待できる。