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論文
- タイトル
- タイトル（英）
- Loss of the sustained antidepressant-like effect of (2R,6R)-hydroxynorketamine in NMDA receptor GluN2D subunit knockout mice.
- 参照URL
- https://researchmap.jp/ikekubo/published_papers/45673659
- 著者
- 著者（英）
- Aimi Yamagishi,Yuiko Ikekubo,Masayoshi Mishina,Kazutaka Ikeda,Soichiro Ide
- 担当区分
- 概要
- 概要（英）
- Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has attracted attention for its acute and sustained antidepressant effects in patients with depression. Hydroxynorketamine (HNK), a metabolite of ketamine, exerts antidepressant effects without exerting ketamine's side effects and has attracted much attention in recent years. However, the detailed pharmacological mechanism of action of HNK remains unclear. We previously showed that the GluN2D NMDA receptor subunit is important for sustained antidepressant-like effects of (R)-ketamine. Therefore, we investigated whether the GluN2D subunit is involved in antidepressant-like effects of (2R,6R)-HNK and (2S,6S)-HNK. Treatment with (2R,6R)-HNK but not (2S,6S)-HNK exerted acute and sustained antidepressant-like effects in the tail-suspension test in wildtype mice. Interestingly, sustained antidepressant-like effects of (2R,6R)-HNK were abolished in GluN2D-knockout mice, whereas acute antidepressant-like effects were maintained in GluN2D-knockout mice. When expression levels of GluN2A and GluN2B subunits were evaluated, a decrease in GluN2B protein expression in the nucleus accumbens was found in stressed wildtype mice but not in stressed GluN2D-knockout mice. These results suggest that the GluN2D subunit and possibly the GluN2B subunit are involved in the sustained antidepressant-like effect of (2R,6R)-HNK.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Journal of pharmacological sciences
- 巻
- 154
- 号
- 3
- 開始ページ
- 203
- 終了ページ
- 208
- 出版年月
- 2024年3月
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.jphs.2024.01.008
- 共同研究・競争的資金等の研究課題
研究者
池窪 結子
(イケクボ ユイコ)