低剂量氯胺酮对工作记忆的影响

氯胺酮是一种N-甲基-D-天冬氨酸受体（NMDAR）阻滞剂,低剂量氯胺酮具有良好的镇痛、抗炎和抗抑郁作用,近年来受到了广泛的关注。但是低剂量氯胺酮对于高级认知功能的影响尚未全面阐明。工作记忆是涉及众多复杂认知活动的关键功能,有研究显示低剂量氯胺酮急性或慢性使用均会损伤工作记忆,其神经机制也开始受到关注。深入分析低剂量氯胺酮对于工作记忆的影响及其机制对于指导氯胺酮的临床使用具有重要意义。本文首先介绍了低剂量氯胺酮作用于神经系统的药理作用途径,以及工作记忆本身的神经环路机制,进而回顾了近年来关于低剂量氯胺酮对工作记忆的急性和慢性作用的相关研究,并重点分析了低剂量氯胺酮损伤工作记忆的可能的神经机制,希望对低剂量氯胺酮在临床中的合理使用提供科学依据。

The Effects of Low Dose Ketamine on Working Memory

Ketamine is an NMDAR antagonist that has been widely used for clinical anesthesia. In addition, low-dose ketamine has analgesic, anti-inflammatory and antidepressant effects, which have attracted extensive attention in recent years. However, how low-dose ketamine can affect the higher cognitive functions remain unclear. Here we review the effects of low-dose ketamine on working memory (WM). WM is the ability to temporally hold and manipulate information in the brain. It mainly relies on a network involving several key brain areas such as the prefrontal cortex (PFC), hippocampus, etc. WM plays a key role in many complex cognitive processes, thus to understand how it may be affected by low-dose ketamine is informative and important for its clinic use. Here we review the studies showing that acute or chronic use of low-dose ketamine will impair working memory in a sophisticated way. The possible mechanisms underlying such impairments include breaking the excitation/inhibition (E/I) balance in the PFC, changing the short-term and long-term synaptic plasticity, activating the DA pathway, etc. We also pointed out that to fully reveal the effects of low-dose ketamine on WM and related neural mechanism, future multi-facet studies combining behavioral tests, electrophysiology, neuroimaging, histology, etc, and with more comparable dosage and time of medication would be needed. We hope that this review will be instrumental for facilitating appropriate use of low-dose ketamine in clinical settings.