Effect of low-dose ketamine combined with propofol anesthesia on expression of GluR1 and GABAA R in hippocampus after electroconvulsive therapy in depressed rats

Abstract

Objective To evaluate the effects of low-dose ketamine combined with propofol anesthesia on the expression of glutamate receptor 1 (GluR1) and γ-aminobutyric acid type A receptor (GABAA R) in hippocampus after electroconvulsive therapy (ECT) in depressed rats.Methods Fifty healthy adult male SpragueDawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.The depressed model was induced by chronic unpredictable mild stress (CUMS).The mentally depressed rats were randomly divided into 5 groups (n =10 each):depression group (group D),ECT group,ketamine + ECT group (group KE),propofol + ECTgroup (group PE) and ketamine + propofol + ECT group (group KPE).Group ECT received ECT once a day for 7 consecutive days after intraperitoneal injection of normal saline 8 ml/kg.KE,PEK and KPE groups received ECT once a day for 7 consecutive days after intraperitoneal injection of ketamine 10 mg/kg,propofol 100 mg/kg,and ketamine 10 mg/kg + propofol 80 mg/kg,respectively.Sucrose fluid consumption was performed before CUMS,at 1 day after CUMS and at 1 day after ECT.The rats were sacrificed and hippocampi were removed for determination of the expression of GluR1 and GABAA R (by immuno-histochemistry).The GluR1/GABAA R ratio was calculated.Results Compared with group D,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA Rratio was increased in the other four groups,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in ECT,PE and KPE groups (P ＜ 0.05).Compared with ECT group,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GABAA R and GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group,the expression of GluR1 and GABAA R in hippocampal CA1 and CA3 regions was up-regulated in KE group,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in PE group (P ＜ 0.05).Compared with group PE,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 and GABAAR in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group (P ＜ 0.05).Conclusion The mechanism by which low-dose ketamine combined with propofol enhances the efficacy of ECT in depressed rats may be related to better regulation of the balance between hippocampal GluR1 and GABAA R. Key words: Depression; Ketamine ; Propofol ; Electroconvulsive therapy ; Receptors, AMPA ; Receptors, GABA-A; Hippocampus