A Reliable High-Throughput Screening Model for Antidepressant

Abstract

Depression is the most frequent affective disorder and is the leading cause of disability worldwide. In order to screen antidepressants and explore molecular mechanisms, a variety of animal models were used in experiments, but there is no reliable high-throughput screening method. Zebrafish is a common model organism for mental illness such as depression. In our research, we established chronic unpredictable mild stress (CUMS) models in C57BL/6 mice and zebrafish; the similarities in behavior and pathology suggest that zebrafish can replace rodents as high-throughput screening organisms. Stress mice (ip., 1 mg/kg/d, 3 days) and zebrafish (10 mg/L, 20 min) were treated with reserpine. As a result, reserpine caused depression-like behavior in mice, which was consistent with the results of the CUMS mice model. Additionally, reserpine reduced the locomotor ability and exploratory behavior of zebrafish, which was consistent with the results of the CUMS zebrafish model. Further analysis of the metabolic differences showed that the reserpine-induced zebrafish depression model was similar to the reserpine mice model and the CUMS mice model in the tyrosine metabolism pathway. The above results showed that the reserpine-induced depression zebrafish model was similar to the CUMS model from phenotype to internal metabolic changes and can replace the CUMS model for antidepressants screening. Moreover, the results from this model were obtained in a short time, which can shorten the cycle of drug screening and achieve high-throughput screening. Therefore, we believe it is a reliable high-throughput screening model.

Development of MAO-A and 5-HT2AR Dual Inhibitors with Improved Antidepressant Activity

“…Among them, lisdexamfetamine is a common and classical depression-inducing drug . Zebrafish is highly sensitive to psychotropic drugs and has become a model species for research in neuroscience fields including depression in recent years, which provides an important perspective for depression drug screening …”

Ten years of unpredictable chronic stress in zebrafish: a systematic review and meta-analysis

“…Most of the records sought for inclusion in either stage of screening were excluded because they did not meet the criteria set for the intervention ( n = 89), followed by the population of interest ( n = 42), and the design of the study ( n = 37). Three studies were excluded from the quantitative analyses because the minimum number of studies to perform a meta-analysis was not reached for the outcomes reported (Zimmermann et al ., 2016; Jayamurali & Govindarajulu, 2017; Marcon et al ., 2018), and four studies were excluded because of missing information (Huang, Butler & Lubin, 2019; Zhang et al ., 2021; Kirsten et al ., 2021; Demin et al ., 2021). This resulted in 31 studies included in the quantitative synthesis.…”

Optimization of Monobenzone-Induced Vitiligo Mouse Model by the Addition of Chronic Stress

“…The open-field test (OFT), forced swimming test (FST), and tail suspension test (TST) were carried out as previously described [ 31 , 49 ]. The OFT was used to observe the behavioral changes in each group of mice and to test the spontaneous activity of the mice.…”