Not so different after all: a systematic review of rodent electroconvulsive therapy (ECT) models in translational chronic stress and depression research

Electroconvulsive therapy (ECT) has been established as an efficacious and safe treatment for severe and/or treatment-resistant depression. However, despite decades of research, the exact biological signature of the mechanism of action of ECT has yet to be elucidated. As a translational tool, electroconvulsive stimulation (ECS), the preclinical rodent equivalent of ECT, offers the unique opportunity for further knowledge under controlled laboratory conditions. Here, for the first time, a systematic review following the PRISMA 2020 statement is presented, covering mouse and rat studies investigating the biobehavioral effects of ECS in chronic stress-based depression models. For this purpose, the PubMed and Web of Science databases (period: 01.01.2000 to 05.10.2023) were screened for different key word combinations (search terms: depression, chronic stress, electroconvulsive shock, rats, mice). The search yielded a total of 1067 records. After filtering, a total of 47 studies were included in this review (n = 7 mice, n = 40 rats). Previous studies have used 4 weeks of chronic unpredictable mild stress (CUMS) in adult male rats treated with bilateral ear clip ECS for 1 week (parameters: bidirectional square wave, 1.5 ms pulse width with 800 mA at 125 Hz, 1.2 sec stimulation duration, 120 mC charge) using no, propofol, or isoflurane anesthesia. The outcome measures were centered around anhedonia-related behaviors and hippocampal protein levels. Summary odds across different behavioral domains revealed antidepressive effects of ECS on anhedonia (14.5), locomotion (6.0), despair (4.3), and anxiety (2.0), accompanied by memory impairments (0.1). Risk of bias assessment suggested considerable risk, primarily due to unreported information on missing data and blinding. Based on our analysis of the evidence, methodological suggestions for future studies were developed. This review will help to further unlock the translational potential of the ECS to generate much needed insights into the molecular correlates of ECT, with special regard to treatment response and prognosis for depression patients.