Time-specific involvement of N-methyl-D-aspartate receptor in the development of schizophrenia-like behavior in rats

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K13965
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental psychology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Furuie Hiroki 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 室長 (90639105)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 統合失調症 / グルタミン酸 / NMDA受容体 / 神経発達障害 / ラット

Outline of Final Research Achievements

In this study, we investigated the effects of neonatal N-methyl-D-aspartate (NMDA) receptor blockade on the expression of schizophrenia-like behaviors in adult rats. First, we investigated the effect of administration of MK-801, an NMDA receptor antagonist, during the second or third postnatal week on spatial memory. MK-801 treatment during the second postnatal week caused severe impairment of spatial working memory. This suggests that neurodevelopmental interference underlying cognitive deficits similar to schizophrenia mainly occurs during this period. Second, we compared the effects of neonatal treatment with an NR2A-preferring antagonist PEAQX and an NR2B-selective antagonist ifenprodil. Neonatal treatment with PEAQX, but not ifenprodil, caused schizophrenia-like behaviors. It is suggested that NR2A-containing NMDA receptor is essential for normal brain development after birth, and the blockade of this receptor in this period induces schizophrenia-like behavior in adulthood.

Free Research Field

実験心理学

Academic Significance and Societal Importance of the Research Achievements

統合失調症の背景にある神経発達障害の発生機序の一端を明らかにできたことにより、同疾患の発症メカニズムの解明に貢献することができた。また本研究の成果は、生後の精神機能の発達を支える神経メカニズムの理解につながる。統合失調症に限らず、認知機能や情動、社会性の障害を抱える広範な発達障害に共通する神経基盤や病態生理の解明と有効な治療法開発の糸口になることが期待される。