Protective Effect of Propofol on Electroconvulsive Shock Induced Learning and Memory Function Impairment Involves Up-Regulation of NMDA Receptor NR2A/2B Subunit in a Rat Model of Depression

Abstract

Backgroud: The mechanism underlying the protective effect of propofol on electroconvulsive therapy (ECT) induced learning and memory function impairment remains largely unknown. The present study aimed to explore the effect of propofol on the expression of N-methyl-D-aspartic acid (NMDA) receptor subunit NR2A/2B and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) in the hippocampus of rat depression model undergoing electroconvulsive shock (ECS, analog of ECT in animals) in order to uncover the mechanism underlying the damaging effect of ECS on the learning and memory function, and the mechanism underlying the protective effect of propofol on the learning and memory function in ECS treatment.Methods: This study was designed as a longitudinal study. Establishment of depression model was conducted with the application of chronic unpredictable mild stress (CUMS) in Sprague-Dawley rats. All 50 rats were randomly assigned into 5 groups (N=10) : one control group ( group C, 10 healthy rats) and four groups exposed to CUMS treatments for 28 days to construct the rat model of depression (group D, P, E, PE). Rats in group C were treated with intraperitoneal injection of 8 ml/kg normal saline and sham ECS (without the administration of current). Rats in group D received intraperitoneal injection of 8 ml/kg normal saline and then sham ECS. Rats in group P received intraperitoneal injection of propofol 80 mg/kg and then sham ECS, while rats in group E were treated with intraperitoneal injection of normal saline 8 ml/kg and then ECS. Rats in group PE were treated with intraperitoneal injection of propofol 80 mg/kg and then ECS. The treatments were conducted once a day for 7 consecutive days. The sucrose preference test was performed to assess the depression behavior. Learning and memory function of rats was evaluated with Morris water maze. Western-blot assay was applied to determine the expression levels of NR2A/2B subunit and GluR1 subunit in the hippocampus.Results: Sucrose preference percentage of the rats in group E and group PE was increased compared with rats in group D. Compared with group D, rats in group E showed increased escape latency, decreased space exploration time, as well as increased expression of GluR1, and decreased NR2A/2B expression. Shorter escape latency, longer space exploration time, and higher level of NR2A/2B expression were showed in rats in group PE than in group E.Conclusions: ECS treatment up-regulated the expression of GluR1 receptor while down-regulated the expression NR2A/2B receptors in rat hippocampus. Propofol mitigating learning and memory function impairment in depression model rats undergoing ECS may via alleviating the inhibitory effect induced by ECS on the NMDA receptor NR2A/2B subunit expression. Citation: Xue-Chao Hao, Xian-Lin Zhu, Ping Li, Jing Chen, Feng Lv, Su Min. Protective effect of propofol on electroconvulsive shock induced learning and memory function impairment involves up-regulation of NMDA receptor NR2A/2B subunit in a rat model of depression. J Anesth Perioper Med 2015; 2: 66-74. doi: 10.24015/JAPM.2015.0011This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.