Identification and pharmacological control of serotonergic projection involved in decision making

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05091
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Kaneko Shuji 京都大学, 薬学研究科, 教授 (60177516)
• Co-Investigator(Kenkyū-buntansha): 永安 一樹 京都大学, 薬学研究科, 助教 (00717902)
• Research Collaborator: Nakagawa Takayuki ; Shirakawa Hisashi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: セロトニン / ウイルスベクター / うつ病

Outline of Final Research Achievements

Major depression is a social and economic burden worldwide. Serotonergic signaling has been implicated in the pathophysiology of this disorder. Moreover, clinical studies have indicated that ketamine has a potent antidepressive efficacy. However, the precise mechanisms underlying major depression are still unclear. Here, we used viral vectors capable of efficient and specific transduction of serotonergic neurons in mice and rats for elucidation of serotonergic roles in depression-like behaviors. We found that ketamine activated dorsal raphe serotonin neurons via activation of acetylcholine neurons in the pedunculopontine tegmental nucleus. We also found that acute activation of serotonergic neurons in the dorsal raphe nucleus increases anti-depressive like behaviors in rats and mice. These findings further our understanding of the pathophysiological role of dorsal raphe serotonergic neurons in different species and the role of these neurons as therapeutic targets in major depression.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

うつ病や不安障害などの精神疾患は、本邦を含む先進国において、極めて重大な社会問題となっている疾患である。本研究は、極めて効果が高いうつ病の治療薬として近年研究が進んでいるケタミンの作用において、アセチルコリン神経核である脚橋被蓋核が極めて重要な役割を果たしている可能性を見出した。また、光遺伝学的手法を用いることで、背側縫線核セロトニン神経を活性化するだけで、抗うつ作用が引き起こされることを明らかにした。