Antidepressants currently used in clinical practice have limitations such as low efficacy, slow onset and various adverse reactions. It has become necessary to develop novel antidepressants beyond monoaminergic drugs. L-701,324 is a potent NMDA receptor antagonist, and the purpose of this study was to investigate the possible antidepressant effects of L-701,324 in mice. Here, various methods including the forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting and immunofluorescence, were used together. A single injection of L-701,324 exhibited antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated injection of L-701,324 not only prevented CUMS-induced depressive-like behaviors in mice, but also ameliorated the downregulating effects of CUMS on the hippocampal BDNF signaling cascade and neurogenesis. Furthermore, K252a, a potent inhibitor of the BDNF system, fully blocked the antidepressant-like activity of L-701,324 in mice. K252a administration also abolished the activating actions of L-701,324 on the hippocampal BDNF signaling cascade and neurogenesis in CUMS-treated mice. Collectively, these data indicated that L-701,324 possesses antidepressant-like activity in mice, which was mediated, at least in part, by promoting the hippocampal BDNF system.

目前临床使用的抗抑郁药存在疗效低、起效慢、不良反应多等局限性。开发单胺能药物以外的新型抗抑郁药已成为必要。L-701,324 是一种有效的 NMDA 受体拮抗剂，本研究的目的是研究 L-701,324 对小鼠可能的抗抑郁作用。在这里，包括强迫游泳试验（FST）、悬尾试验（TST）、慢性不可预测轻度应激（CUMS）抑郁症模型、蛋白质印迹和免疫荧光在内的各种方法被结合使用。单次注射 L-701,324 在 FST 和 TST 中表现出类似抗抑郁药的潜力，而不会影响小鼠的运动活动。重复注射 L-701,324 不仅可以防止小鼠 CUMS 诱导的抑郁样行为，但也改善了 CUMS 对海马 BDNF 信号级联和神经发生的下调作用。此外，BDNF 系统的强效抑制剂 K252a 完全阻断了小鼠体内 L-701,324 的抗抑郁样活性。K252a 给药还消除了 L-701,324 对 CUMS 治疗小鼠海马 BDNF 信号级联和神经发生的激活作用。总的来说，这些数据表明 L-701,324 在小鼠体内具有抗抑郁样活性，这至少部分是由促进海马 BDNF 系统介导的。324 对 CUMS 治疗小鼠的海马 BDNF 信号级联和神经发生的影响。总的来说，这些数据表明 L-701,324 在小鼠体内具有抗抑郁样活性，这至少部分是由促进海马 BDNF 系统介导的。324 对 CUMS 治疗小鼠的海马 BDNF 信号级联和神经发生的影响。总的来说，这些数据表明 L-701,324 在小鼠体内具有抗抑郁样活性，这至少部分是由促进海马 BDNF 系统介导的。