Neural activity recording in striatum at novel onset model of schizophrenia

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20849
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Umemoto Sachio 東京大学, 大学院医学系研究科(医学部), 特任研究員 (30967469)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: ドーパミン / 線条体 / D2細胞 / メタンフェタミン / 統合失調症

Outline of Final Research Achievements

The purpose of this study was to establish a novel onset model of schizophrenia in which dysfunction of striatal D2 cells causes schizophrenia-like behavior, and to elucidate the neural activity in the pathological state by measuring dopamine amount in the striatum. In the first year, I established a novel model of schizophrenia onset by inducing "abnormal behavior" in 3CSRTT, a kind of operant learning task, under methamphetamine sensitization. In the final year, I conducted dopamine measurements in nucleus accumbens, a part of ventral striatum, in the environment in which the reward context was removed from the task. The results suggested that dopamine increases in task-related behavior in the absence of reward. Behavioral results also showed that administration of D2 blocker during the task suppressed the occurrence of "abnormal" behavior.

Free Research Field

神経行動学

Academic Significance and Societal Importance of the Research Achievements

本研究は、統合失調症の病態に基づき、かつ行動指標の時系列における変化を軸にした新規発症モデルを構築した。これまでの研究では行動の量的な変動に関する議論に留まっていたため、病態との質的な一致を基に発生機序を議論できるという点で新しい。また、発症までの時系列を追跡した手法であるため、段階に分けた介入方法の検証もより容易となっている。このことは、統合失調症やその他精神疾患における新しい治療法の開発に役立つと考えられる。