Anesthetics alleviate learning and memory impairment induced by electroconvulsive shock by regulation of NMDA receptor-mediated metaplasticity in depressive rats

作者：Ren, Li; Hao, Xuechao; Min, Su^*; Deng, Jie; Chen, Qibin; Chen, Hengsheng; Liu, Dawei

来源：Neurobiology of Learning and Memory, 2018, 155: 65-77.

DOI：10.1016/j.nlm.2018.06.013

• Electroconvulsive therapy
• Propofol
• Ketamine
• Metaplasticity
• Learning
• Memory

Along with its outstanding antidepressant effect, electroconvulsive shock (ECS) can induce learning and memory impairment. Propofol and ketamine have shown to be useful in alleviating the learning and memory impairment. Nevertheless, the mechanism still remains unclear. This study investigated the role of NMDA receptor (NMDAR)mediated metaplasticity in the learning and memory impairment induced by ECS, as well as the neuroprotective effect of propofol and ketamine in depressive rats. Rats received ECS or ECS under anesthetics after chronic unpredictable mild stress procedure. Long-term potentiation (LTP) was tested by extracellular recording. LTD/LTP threshold was assessed by stimulation of different frequencies. Additionally, NMDAR-mediated field excitatory postsynaptic potential (fEPSP) and NMDAR input/output relationship were detected under hippocampal slice perfusion. Results showed that propofol or low-dose ketamine could partially alleviate ECS-induced LTP impairment, while propofol combined with low-dose ketamine almost reversed the LTP impairment. LTP under ECS was increased by stronger stimulation. ECS could up-regulated LTD/LTP threshold, while propofol or ketamine could down-regulate it. Moreover, ECS activated NMDAR, while propofol and ketamine could inhibit the activation of NMDAR. NMDAR input/output relationship decrease was induced by preconditioning (an analog of ECS in hippocampal slice), however, NMDAR input/output relationship increased by propofol or ketamine. In conclusion, ECS-induced cognitive impairment is caused by NMDAR-mediated metaplasticity via up-regulation of LTD/LTP threshold. Propofol or ketamine alleviates the cognitive impairment, possibly by down-regulating the threshold via inhibition of NMDAR activation induced by ECS.

• 出版日期2018-11
• 单位重庆医科大学