Effects of Diazepam and Nortriptyline on Behavioral Changes and Chronic Stress-Induced Depression in Zebrafish (Danio rerio)

Najarzadeh, Mohadeseh; Changizi, Reza; Manouchehri, Hamed; Siahposht Khachaki, Ali

doi:10.22124/japb.2025.30222.1566

Effects of Diazepam and Nortriptyline on Behavioral Changes and Chronic Stress-Induced Depression in Zebrafish (Danio rerio)

Articles in Press

Document Type : Research Paper

Authors

¹ Doctor of Veterinary Medicine, Babol Branch, Islamic Azad University, Babol, Iran

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

³ Department of Veterinary, Babol Branch, Islamic Azad University, Babol, Iran

⁴ Department of Physiology, Mazandaran University of Medical Science, Sari, Iran

10.22124/japb.2025.30222.1566

Abstract

Depression is a mental disorder that is becoming increasingly prevalent, highlighting the growing need for research on depression models and the development of novel antidepressant drugs. This study aimed to evaluate the individual and combined effects of diazepam and nortriptyline on behavioral and biochemical parameters in zebrafish (Danio rerio). To induce depression, the Unpredictable Chronic Stress (UCS) protocol was employed. Behavioral assessments were conducted using the Novel Tank Test (NTT), and biochemical analyses involved measuring whole-body cortisol levels. Diazepam and nortriptyline significantly improved behavioral parameters, as evidenced by a marked increase in the duration of time spent in the upper zone and the number of transitions to the upper zone, along with a significant reduction in total distance traveled. Additionally, these treatments effectively mitigated depression-like behaviors by significantly lowering cortisol levels (from 1.01 ± 0.07 to 0.38 ± 0.16 ng). The findings of this study corroborate previous data, demonstrating that the UCS protocol induces behavioral and neuroendocrine alterations in zebrafish, which can be prevented by diazepam and nortriptyline administration. Furthermore, this study reinforces the utility of zebrafish as a model organism for investigating the behavioral and physiological effects of stress.

Keywords