Studying the Stress, Gene Expression, and Behavioral Changes Induced by Diazepam and Sertraline in a Zebrafish Model

The high global prevalence of depression and its growing impact highlight an urgent need for better models and antidepressant treatments. Hence, in the present research, the effects of the anxiolytic drug diazepam and the antidepressant sertraline on behavioral, biochemical, and molecular parameters in zebrafish (Danio rerio) were investigated using the Unpredictable Chronic Stress (UCS) protocol. The Novel Tank Test (NTT) was used to evaluate the behavioral changes, while biochemical analysis was performed by cortisol measurement. Molecular analysis of proinflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10) cytokine gene expression was also performed using RT-PCR. The acquired data were analyzed using two-way ANOVA in SPSS software. It was found that the UCS protocol induced significant behavioral and neuroendocrine alterations. Treatment with diazepam, sertraline, and their combination led to significant improvements in behavioral outcomes, as indicated by increased time spent and number of entries in the top zone of the tank. Additionally, these treatments reduced the expression of inflammatory cytokine genes (TNF-α, IL-6), such that sertraline showed a significant reduction in cortisol levels (from 1.01 ± 0.07 ng/g to 0.15 ± 0.04 ng/g). These findings reinforce the utility of the zebrafish model for elucidating stress-induced pathophysiology and validate the UCS protocol as a robust method for assessing potential treatments of psychiatric therapeutics.