School of Biological Sciences, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2- 1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
Mol Brain. 2021 Dec 7;14(1):174. doi: 10.1186/s13041-021-00883-7.
Ketamine, a non-competitive antagonist of the N-methyl-D-aspartate receptor (NMDAR), generates a rapidly-acting antidepressant effect. It exerts psychomimetic effects, yet demands a further investigation of its mechanism. Previous research showed that ketamine did no longer promote hyperlocomotion in GluN2D knockout (KO) mice, which is a subunit of NMDAR. In the present study, we tested whether GluN2D-containing NMDARs participate in the physiological changes in the medial prefrontal cortex (mPFC) triggered by ketamine. Sub-anesthetic dose of ketamine (25 mg/kg) elevated the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in wild-type (WT) mice, but not in GluN2D KO mice, 1 h after the injection. The amplitude of sEPSC and paired-pulse ratio (PPR) were unaltered by ketamine in both WT and GluN2D KO mice. These findings suggest that GluN2D-containing NMDARs might play a role in the ketamine-mediated changes in glutamatergic neurons in mPFC and, presumably, in ketamine-induced hyperlocomotion.
氯胺酮是一种 N-甲基-D-天冬氨酸受体（NMDAR）的非竞争性拮抗剂，能迅速产生抗抑郁作用。它具有致幻作用，但需要进一步研究其作用机制。先前的研究表明，氯胺酮不再促进 NMDAR 亚基 GluN2D 敲除（KO）小鼠的过度活跃，在本研究中，我们测试了 GluN2D 包含的 NMDAR 是否参与氯胺酮引发的内侧前额叶皮层（mPFC）的生理变化。亚麻醉剂量的氯胺酮（25mg/kg）在注射后 1 小时，可增加野生型（WT）小鼠而非 GluN2D KO 小鼠的自发兴奋性突触后电流（sEPSC）频率。sEPSC 的幅度和成对脉冲比（PPR）在 WT 和 GluN2D KO 小鼠中均未受氯胺酮影响。这些发现表明，GluN2D 包含的 NMDAR 可能在氯胺酮介导的 mPFC 谷氨酸能神经元变化中发挥作用，可能在氯胺酮诱导的过度活跃中发挥作用。
