Effect of neonatal NMDA receptor chronically blockade on time perception and on its neural mechanism in rats

Research Project

Project/Area Number	17K17992
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Experimental psychology Psychiatric science
Research Institution	Yokohama City University
Principal Investigator	NIIKURA Ryo 横浜市立大学, 医学研究科, 特任助教 (70760750)
Project Period (FY)	2017-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	時間知覚 / 統合失調症 / 疾患モデル動物 / 行動実験 / NMDA受容体 / 新生仔期 / ラット / オペラント条件づけ / 行動学 / 生理学 / 神経科学 / 精神生物学
Outline of Final Research Achievements	In the present study, we evaluated the temporal information processing of neonatal N-methyl-D-aspartate receptor（NMDAR）blockade rat, a model rats of schizophrenia, and aimed to identify the neural mechanisms that contribute to its abnormalities. This model rats exhibited abnormal temporal information processing similar to schizophrenia patients in the temporal bisection task, but not time reproduction task. Contrary to expectations, no changes were observed in the dopaminergic system in the animals, while an increment in neural activity in the medial prefrontal cortex during temporal perception was observed. These results suggest that neonatal NMDAR blockade rats were potential animal model of schizophrenia that involve abnormal temporal cognition. Furthermore, temporal information processing abnormalities in this animal, and even in schizophrenia, may be caused by alternation in attentional function, but mediated by something other than the dopaminergic system.
Academic Significance and Societal Importance of the Research Achievements	統合失調症は、原因や治療法など未解明な点が多い精神疾患である。この問題の解明のためには、妥当性の高いモデル動物の確立が必要とされる。近年、統合失調症患者の秒単位の時間情報処理（時間知覚）の異常が報告されているが、疾患モデル動物の時間知覚機能は今まで明らかにされていない。本研究は、統合失調症のモデル動物が統合失調症患者と類似した時間知覚機能の異常を示すことを明らかにし、同動物の疾患モデル動物としての有用性を高めた。一方、時間知覚課題遂行中の同動物にドーパミン神経系の異常は認められず、統合失調症の時間知覚異常がドーパミンに依存しないものである可能性を示した。