Effects of Diazepam and Escitalopram on Stress and Gene Expression in Zebra Fish (Danio rerio) as Human Model

Document Type : Research Paper

Authors
Ali Tahamtannezhad Emran 1
Hamed Manouchehri 2
Reza Changizi 1
Shahab Tirgar Fakheri 1
Mohadeseh Najarzadeh 1
Meysam Rameshgar 1
1 Veterinary Department, Islamic Azad University, Babol branch, Babol, Iran
2 Department of Veterinary, Islamic Azad University, Babol branch, Babol, Iran
10.22034/cmr.2025.8588.3318
Abstract
Depression is a mental disorder that is becoming increasingly prevalent, highlighting the growing need for research on depression models and the development of antidepressant drugs. This study aimed to evaluate the individual and combined effects of Diazepam and Escitalopram on behavioral and biochemical parameters in zebrafish (Danio rerio). To induce depression in zebrafish, the Unpredictable Chronic Stress (UCS) protocol was applied. Biochemical assays were conducted by measuring cortisol levels using the ELISA technique, while molecular analyses assessed the expression of pro-inflammatory and anti-inflammatory cytokine genes using Real-time PCR. Data were analyzed with SPSS software using the Kolmogorov-Smirnov test and two-way repeated measures ANOVA. Diazepam, Escitalopram, and their combination significantly prevented depressive effects by markedly reducing the expression of pro-inflammatory cytokine genes (tnf-α, il-6) and lowering cortisol levels (from 1.01±0.07 ng/g tissue to 0.61±0.12 ng/g tissue). This study confirmed previous findings indicating that the UCS protocol induces distinct neuroendocrine alterations in zebrafish, which can be mitigated by sedative and antidepressant drugs. Furthermore, the research reinforced the utility of zebrafish as a model organism in behavioral and physiological stress studies, demonstrating that the UCS protocol is a valuable experimental tool for evaluating novel drugs targeting stress-related psychiatric disorders.
Keywords
Depression
Zebrafish
Diazepam
Escitalopram
UCS Protocol
Journal of Animal Research (Iranian Journal of Biology)
Volume 38, Issue 3
Autumn 2025
Pages 232-250

  • Receive Date 27 January 2025
  • Revise Date 14 June 2025
  • Accept Date 17 August 2025