Effect of different charges of modified electroconvulsive seizure on the cognitive behavior in stressed rats: Effects of GluR1 phosphorylation and CaMKIIα activity

摘要

Electroconvulsive therapy (ECT) is an efficient therapy for major depression and modern ECT requires anesthesia to enhance safety. However, the commonly used anesthetic, propofol, may weaken the treatment efficacy. A recent study confirmed that ketamine rapidly reduced the symptoms of depression in affected patients. A previous study found that electroconvulsive seizure (ECS), the animal model for ECT, under anesthesia of low-dose ketamine combined with propofol could enhance the antidepressant efficacy and improve the cognitive performance. The present study aimed to investigate the responses to different charges (0, 60, 120, 180 or 240 mC) of ECS under compound anesthetics, ketamine combined with propofol, in stressed rats and the underlying mechanisms to aid in optimization of treatment regimens. The results indicated that ECS exhibited an improved antidepressant effects at 120 mC compared with 60 mC, however, no significant differences in antidepressant effects were identified among the 120, 180 and 240 mC groups. Furthermore, rats subjected to ECS at 120 mC exhibited the best cognitive performance. The phosphorylation levels of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) at Thr286, glutamate receptor 1 (GluR1) at Ser831 and cAMP-response element-binding protein (CREB) at the Ser133 were higher in the 120-mC group compared with all other groups. These results indicated that the ECS at medium intensity (120 mC) with administration of compound anesthetics may exert an improved therapeutic effect on depression compared with other intensities (0, 60, 180 and 240 mC). The results also suggested that the improvement in cognitive function in stressed rats may be attributed to the phosphorylation of CaMKIIα (Thr286), GluR1 (Ser831) and CREB (Ser133).