Identification of neural substrate for pathological habit

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K10270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Showa University
• Principal Investigator: TODA SHIGENOBU 昭和大学, 医学部, 准教授 (00323006)
• Co-Investigator(Kenkyū-buntansha): 西川 宏美 金沢大学, 医学系, 研究員 (70534155)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 習慣 / 注意 / 目標指向性行動 / 線条体 / 最初期遺伝子

Outline of Final Research Achievements

First, we confirmed that the alteration of immediate early gene expression in the entire rat striatum during an operant training was mainly processed in Dopamine D1-positive medium spiny neurons. We next tried to ease sustained attentional load during a fixed interval schedule of operant training in rats and found this treatment promoted habit formation. Thus, we concluded that sustained attention to measure temporal intervals may suppress habit development. Third, we aimed to reveal the functional significance of c-fos positive neurons in the rat amygdala in behavioral augmentation and habit formation during operant training. A compound that specifically disrupts c-fos positive cells resulted in the attenuation of behavioral augmentation when treated in the central amygdala, whereas it suppressed habit formation when treated in the basolateral amygdala. Therefore, it is suggested that these two amygdala subregions may play distinct roles in operant training.

Free Research Field

意思決定、依存症

Academic Significance and Societal Importance of the Research Achievements

行動の過剰な促進化や習慣化は、依存症や強迫性障害、ギャンブル障害など様々な精神疾患で問題となっており、その病態機序の解明と治療法の開発は急務である。本研究の結果、習慣化における持続性注意の意義が明らかとなった。これは注意の持続に障害を有する ADHDなどで不適切な習慣化が起きやすい可能性を示唆する。また、扁桃体での異なる領域が、行動の促進化と習慣化に関して独自に関与することが示唆された。この結果は、行動の促進化と習慣化を個別に制御できる可能性を示唆しており、例えば将来的には習慣化を阻害することなく、不適切な行動の異常促進だけを抑制する治療法の開発につながる可能性がある。