Investigation of the Effects of Diazepam and Sertraline on Gene Expression and Depression Induced by Chronic Stress in Zebrafish (Danio rerio) as Human Model

Tirgar Fakheri, Shahab; Changizi, Reza; Manouchehri, Hamed; Tahamtan Nezhad Emran, Ali; Najarzadeh Ahangarkolaei, Mohadeseh; Rameshgar, Meysam

doi:10.22075/jvlr.2026.37436.1162

Investigation of the Effects of Diazepam and Sertraline on Gene Expression and Depression Induced by Chronic Stress in Zebrafish (Danio rerio) as Human Model

Articles in Press

Document Type : Original Article

Authors

Shahab Tirgar fakheri ¹

Reza Changizi ¹

Hamed Manouchehri ¹

Ali Tahamtan nezhad emran ¹

Mohadeseh Najarzadeh Ahangarkolaei ¹

Meysam Rameshgar ²

¹ Department of Veterinary, Babol branch, Islamic Azad University, Babol, Iran

² Department of Biology, Babol branch, Islamic Azad University, Babol, Iran

10.22075/jvlr.2026.37436.1162

Abstract

Depression is a mental disorder that currently affects a significant portion of the global population. According to statistics, this issue is becoming increasingly severe, highlighting the growing need for research on depression models and the development of antidepressant medications.
The aim of this study was to evaluate the effects of diazepam and sertraline on biochemical and molecular parameters in zebrafish (Danio rerio) using the Unpredictable Chronic Stress (UCS) protocol.
Biochemical tests were conducted by measuring cortisol levels, while molecular tests involved analyzing the expression of pro-inflammatory and anti-inflammatory cytokine genes.
The results of this study show that diazepam, sertraline, and their combination significantly prevent depressive effects by significantly reducing the expression levels of pro-inflammatory cytokine genes (TNF-α, IL-6) and significantly decreasing cortisol levels (from approximately 1 ng of cortisol per gram of tissue to approximately 0.25 ng per gram of tissue).
This research confirms previous data showing that the UCS protocol induces behavioral and neuroendocrine changes in zebrafish, which can be prevented with diazepam and sertraline. Additionally, this study reinforces the use of zebrafish as a model organism in studies of the behavioral and physiological impacts of stress.

Keywords

Depression

Diazepam

Sertraline

Zebrafish

UCS Protocol

Subjects