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論文
- タイトル
- タイトル（英）
- Understanding the role of the
NMDA receptor subunit,GluN2D , in mediatingNMDA receptor antagonist‐induced behavioral disruptions in male and female mice - 参照URL
- https://researchmap.jp/read0201960/published_papers/43931808
- 著者
- 著者（英）
- Chitra Vinnakota,Anna Schroeder,Xin Du,Kazutaka Ikeda,Soichiro Ide,Masayoshi Mishina,Matthew Hudson,Nigel Charles Jones,Suresh Sundram,Rachel Anne Hill
- 担当区分
- 概要
- 概要（英）
- Abstract Noncompetitive NMDA receptor (NMDAR) antagonists like phencyclidine (PCP) and ketamine cause psychosis‐like symptoms in healthy humans, exacerbate schizophrenia symptoms in people with the disorder, and disrupt a range of schizophrenia‐relevant behaviors in rodents, including hyperlocomotion. This is negated in mice lacking the GluN2D subunit of the NMDAR, suggesting the GluN2D subunit mediates the hyperlocomotor effects of these drugs. However, the role of GluN2D in mediating other schizophrenia‐relevant NMDAR antagonist‐induced behavioral disturbances, and in both sexes, is unclear. This study aimed to investigate the role of the GluN2D subunit in mediating schizophrenia‐relevant behaviors induced by a range of NMDA receptor antagonists. Using both male and female GluN2D knockout (KO) mice, we examined the effects of the NMDAR antagonist's PCP, the S‐ketamine enantiomer (S‐ket), and the ketamine metabolite R‐norketamine (R‐norket) on locomotor activity, anxiety‐related behavior, and recognition and short‐term spatial memory. GluN2D‐KO mice showed a blunted locomotor response to R‐norket, S‐ket, and PCP, a phenotype present in both sexes. GluN2D‐KO mice of both sexes showed an anxious phenotype and S‐ket, R‐norket, and PCP showed anxiolytic effects that were dependent on sex and genotype. S‐ket disrupted spatial recognition memory in females and novel object recognition memory in both sexes, independent of genotype. This datum identifies a role for the GluN2D subunit in sex‐specific effects of NMDAR antagonists and on the differential effects of the R‐ and S‐ket enantiomers.
- 出版者・発行元
- 出版者・発行元（英）
- Wiley
- 誌名
- 誌名（英）
- Journal of Neuroscience Research
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2023年10月10日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 0360-4012
- DOI URL
- https://doi.org/10.1002/jnr.25257
- 共同研究・競争的資金等の研究課題